US8900630B2 - Microcapsules having multiple shells and method for the preparation thereof - Google Patents

Microcapsules having multiple shells and method for the preparation thereof Download PDF

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US8900630B2
US8900630B2 US13009418 US201113009418A US8900630B2 US 8900630 B2 US8900630 B2 US 8900630B2 US 13009418 US13009418 US 13009418 US 201113009418 A US201113009418 A US 201113009418A US 8900630 B2 US8900630 B2 US 8900630B2
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shell
microcapsules
shells
step
gelatine
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Nianxi Yan
Yulai Jin
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DSM Nutritional Products AG
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DSM Nutritional Products AG
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5015Organic compounds, e.g. fats, sugars
    • A23L1/0029
    • A23L1/22016
    • A23L1/3008
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A23B - A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/70Fixation, conservation, or encapsulation of flavouring agents
    • A23L27/72Encapsulation
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A23B - A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12Fatty acids or derivatives thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23PSHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00Shaping or working of foodstuffs characterised by the products
    • A23P10/30Encapsulation of particles, e.g. foodstuff additives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5052Proteins, e.g. albumin
    • A61K9/5057Gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5089Processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02Making microcapsules or microballoons
    • B01J13/06Making microcapsules or microballoons by phase separation
    • B01J13/10Complex coacervation, i.e. interaction of oppositely charged particles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02Making microcapsules or microballoons
    • B01J13/20After-treatment of capsule walls, e.g. hardening
    • B01J13/22Coating
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES
    • A23V2200/00Function of food ingredients
    • A23V2200/20Ingredients acting on or related to the structure
    • A23V2200/224Encapsulating agent
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES
    • A23V2250/00Food ingredients
    • A23V2250/18Lipids
    • A23V2250/186Fatty acids
    • A23V2250/1868Docosahexaenoic acid
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES
    • A23V2250/00Food ingredients
    • A23V2250/18Lipids
    • A23V2250/186Fatty acids
    • A23V2250/187Eicosapentaenoic acid
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES
    • A23V2250/00Food ingredients
    • A23V2250/54Proteins
    • A23V2250/542Animal Protein
    • A23V2250/5432Gelatine
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00Stock material or miscellaneous articles
    • Y10T428/29Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
    • Y10T428/2982Particulate matter [e.g., sphere, flake, etc.]
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00Stock material or miscellaneous articles
    • Y10T428/29Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
    • Y10T428/2982Particulate matter [e.g., sphere, flake, etc.]
    • Y10T428/2984Microcapsule with fluid core [includes liposome]
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00Stock material or miscellaneous articles
    • Y10T428/29Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
    • Y10T428/2982Particulate matter [e.g., sphere, flake, etc.]
    • Y10T428/2984Microcapsule with fluid core [includes liposome]
    • Y10T428/2985Solid-walled microcapsule from synthetic polymer
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00Stock material or miscellaneous articles
    • Y10T428/29Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
    • Y10T428/2982Particulate matter [e.g., sphere, flake, etc.]
    • Y10T428/2989Microcapsule with solid core [includes liposome]

Abstract

Single-core and multi-core microcapsules are provided, having multiple shells, at least one of which is formed of a complex coacervate of two components of shell materials. The complex coacervate may be the same or different for each shell. Also provided are methods for making the microcapsules.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No. 12/642,303, filed Dec. 18, 2009, and which is a continuation of U.S. application Ser. No. 10/497,290, filed Nov. 4, 2003, now abandoned, and which claims the benefit of priority to U.S. Provisional Patent Application No. 60/423,363 filed Nov. 4, 2002, which applications are incorporated by reference herein in their entireties.

FIELD OF THE INVENTION

This invention relates to microcapsules having multiple shells, to methods of preparing microcapsules and to their use.

BACKGROUND OF THE INVENTION

Microcapsules are small particles of solids, or droplets of liquids, inside a thin coating of a shell material such as starch, gelatine, lipids, polysaccharides, wax or polyacrylic acids. They are used, for example, to prepare liquids as free-flowing powders or compressed solids, to separate reactive materials, to reduce toxicity, to protect against oxidation and/or to control the rate of release of a substance such as an enzyme, flavour, a nutrient, a drug, etc.

Ideally, a microcapsule would have good mechanical strength (e.g. resistance to rupture) and the microcapsule shell would provide a good barrier to oxidation, etc.

A typical approach to meeting these requirements is to increase the thickness of the microcapsule wall. But this results in an undesirable reduction in the loading capacity of the microcapsule. That is, the “payload” of the microcapsule, being the mass of the loading substance encapsulated in the microcapsule divided by the total mass of the microcapsule, is low. The typical payload of such “single-core” microcapsules made by spray drying an emulsion is in the range of about 25-50%.

Another approach to the problem has been to create what are known as “multi-core” microcapsules. These microcapsules are usually formed by spray drying an emulsion of core material such that the shell material coats individual particles of core material, which then aggregate and form a cluster. A typical multi-core microcapsule is depicted in prior art FIG. 1. Multi-core microcapsule 10 contains a plurality of cores 12. The cores 12 take the form of entrapped particles of solids or of liquid droplets dispersed throughout a relatively continuous matrix of shell material 14. As a result, there is a high ratio of shell material to loading material and the payload of the multi-core microcapsule is therefore low. Moreover, despite the high ratio of shell material to loading substance in such microcapsules, the shell material is poorly distributed. As shown in prior art FIG. 1, many of the cores 12 are very close to the surface 16 of the microcapsule. The cores at the surface are therefore not well protected against rupture or from oxidation.

Known microcapsules therefore either have a poor payload, or fail to adequately contain and protect the loading substance deposited therein. Moreover, because these microcapsules are generally prepared in a single step, it is difficult to incorporate multiple functionalities, such as oxidation resistance, moisture resistance and taste masking into a single microcapsule.

SUMMARY OF THE INVENTION

In one aspect, the invention provides a multi-core microcapsule comprising: (a) an agglomeration of primary microcapsules, each primary microcapsule comprising a core and a first shell surrounding the core; (b) a second shell surrounding the agglomeration; and (c) a third shell surrounding the second shell; at least one of the first, second and third shells comprising a complex coacervate.

In another aspect, the invention provides a single-core microcapsule comprising: (a) a core; (b) a first shell surrounding the core; and (c) a second shell surrounding the first shell; at least one of the first and second shells comprising a complex coacervate.

In the case of either the multi-core or single-core microcapsules, it is preferred that all of the shells comprise a complex coacervate, which may be the same or different for each of the shells. Additional shells, e.g. from 1 to 20, may be added to further strengthen the microcapsule.

In another aspect, the invention provides a process for making a microcapsule having a plurality of shells, the process comprising:

  • (a) providing a microcapsule selected from the group consisting of:
    • (i) a multi-core microcapsule comprising: an agglomeration of primary microcapsules, each primary microcapsule comprising a core and a first shell surrounding the core; and a second shell surrounding said agglomeration; and
    • (ii) a single-core microcapsule comprising: a core; and a first shell surrounding the core;
  • (b) mixing the microcapsule with first and second polymer components of shell material in aqueous solution;
  • (c) adjusting at least one of pH, temperature, concentration and mixing speed to form shell material comprising the first and second polymer components, the shell material forming an additional shell enveloping the microcapsule;
    wherein at least one of the first shell, the second shell and the additional shell comprises a complex coacervate.
BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a typical prior art multi-core microcapsule.

FIGS. 2 and 3 depict embodiments of the invention in which multi-core microcapsules are provided having multiple shells.

FIGS. 4 and 5 depict embodiments of the invention in which single-core microcapsules are provided having multiple shells.

FIG. 6 is a photomicrograph of multi-core microcapsules prepared with a one-step process (62% payload), prepared for purposes of comparison.

FIG. 7 is a photomicrograph of multi-core microcapsules prepared with a two-step process in accordance with the invention (59% payload).

FIG. 8 is a photomicrograph of multi-core microcapsules prepared with a two-step process in accordance with the invention in which alginate is incorporated in the outer shell (53% payload).

FIG. 9 is a photomicrograph of multi-core microcapsules prepared with a three-step process in which lipids and alginate are incorporated in an inner shell while gelatine and polyphosphate forms an outer shell.

FIG. 10 is a photomicrograph of multi-core microcapsules prepared with a two-step process in which lipids and alginate are incorporated in the second shell.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Core Materials

Any core material that may be encapsulated in microcapsules is useful in the invention. Indeed, in certain embodiments, commercially available microcapsules may be obtained and then further processed according to the processes of the invention.

When the initial multi-core microcapsules are prepared according to processes as described herein involving an aqueous solution, the core material may be virtually any substance that is not entirely soluble in the aqueous solution. Preferably, the core is a solid, a hydrophobic liquid, or a mixture of a solid and a hydrophobic liquid. The core is more preferably a hydrophobic liquid, such as grease, oil or a mixture thereof. Typical oils may be fish oils, vegetable oils, mineral oils, derivatives thereof or mixtures thereof. The loading substance may comprise a purified or partially purified oily substance such as a fatty acid, a triglyceride or a mixture thereof. Omega-3 fatty acids, such as α-linolenic acid (18:3n3), octadecatetraenoic acid (18:4n3), eicosapentaenoic acid (20:5n3) (EPA) and docosahexaenoic acid (22:6n3) (DHA), and derivatives thereof and mixtures thereof, are preferred. Many types of derivatives are well known to one skilled in the art. Examples of suitable derivatives are esters, such as phytosterol esters, branched or unbranched C1-C30 alkyl esters, branched or unbranched C2-C30 alkenyl esters or branched or unbranched C3-C30 cycloalkyl esters, in particular phytosterol esters and C1-C6 alkyl esters. Preferred sources of oils are oils derived from aquatic organisms (e.g. anchovies, capelin, Atlantic cod, Atlantic herring, Atlantic mackerel, Atlantic menhaden, salmonids, sardines, shark, tuna, etc) and plants (e.g. flax, vegetables, algae, etc).

While the core may or may not be a biologically active substance such as a tocopherol, antioxidant or vitamin, the microcapsules of the present invention are particularly suited for biologically active substances, for example, drugs, nutritional supplements, flavours, antioxidants or mixtures thereof.

Shell Material

Coacervation is a phase separation phenomenon, in which a homogenous polymer solution is converted into two phases. One is a polymer-rich phase, called a coacervate. The other is a polymer-poor phase, i.e., solvent. Complex coacervation is caused by the interaction of two oppositely charged polymers.

Preferably, a positively charged polymer component “A” interacts with a negatively charged polymer component “B”. For example, positively charged type A gelatine (“component A”) forms complex coacervates with negatively charged polyphosphate (“component B”). Other systems that have been studied are gelatine/gum Acacia, gelatine/pectin, gelatine/carboxymethyl guar gum and whey protein/gum arabic.

Component A is preferably gelatine type A, chitosan, etc., although other polymers are also contemplated as component A. Component B is preferably gelatine type B, polyphosphate, gum arabic, alginate, carrageenan, pectin, carboxymethylcellulose, or a mixture thereof.

In addition to the charge density of the two polymer components, complex coacervation depends on other factors such as molecular weight of the polymers and their ratio, ionic strength, pH and temperature of the medium (J. Microencapsulation, 2003, Vol. 20, No. 2: 203-210).

The molar ratio of component A:component B that is used depends on the type of components but is typically from 1:5 to 15:1. For example, when gelatine type A and polyphosphate are used as components A and B respectively, the molar ratio of component A:component B is preferably 8:1 to 12:1; when gelatine type A and gelatine type B are used as components A and B respectively, the molar ratio of component A:component B is preferably 2:1 to 1:2; and when gelatine type A and alginate are used as components A and B respectively, the molar ratio of component A:component B is preferably 3:1 to 5:1.

One suitable process of microencapsulation using complex coacervation comprises three steps: 1) dispersing the loading substance into a system of at least one of the polymers for the complex coacervate; 2) forming shells by deposition of coacervates which derive from the polymeric components under controlled conditions of temperature, pH, concentration of colloids, mixing speed etc.; and 3) hardening of the shells by crosslinking of the coacervates deposited on microcapsules (Ullmann's Encyclopedia of Industrial Chemistry 6th edition. 2001, Vol. A16. pp. 575-588).

Any shells that do not comprise complex coacervates may be formed of any material that can form an additional shell around the microcapsule. The additional shell material typically comprises at least one polymer component. Examples of polymer components include, but are not limited to, proteins, e.g. gelatines, soy proteins, whey proteins, and milk proteins, polyphosphate, polysaccharides and mixtures thereof. Preferred polymer components are gelatine A, gelatine B, polyphosphate, gum arabic, alginate, chitosan, carrageenan, pectin, cellulose or derivatives of cellulose such as carboxymethylcellulose (CMC) or a mixture thereof. A particularly preferred form of gelatine type A has a Bloom strength of 50-350, more preferably a Bloom strength of about 275.

The shell material can also comprise lipids, such as waxes, fatty acids and oils, etc. to provide desired functionalities. The incorporation of lipids into the shell material improves the impermeability of the shell to water and oxygen. A preferred lipid for this purpose is beeswax. These lipids may be in solid, semi-solid or liquid form.

Processing Aids

Processing aids may be included in the shell material. Processing aids may be used for a variety of reasons. For example, they may be used to promote agglomeration of primary microcapsules when forming multi-core microcapsules, control microcapsule size and shape and/or to act as an antioxidant. Antioxidant properties are useful both during the process (e.g. during coacervation and/or spray drying) and in the microcapsules after they are formed (e.g. to extend shelf-life of loading substances which are readily oxidized, etc). Preferably a small number of processing aids that perform a large number of functions are used. For example, ascorbic acid or a salt thereof may be used to promote agglomeration of the primary microcapsules, to control microcapsule size and shape and to act as an antioxidant. The ascorbic acid or salt thereof is preferably used in an amount of about 100 ppm to about 10,000 ppm, more preferably about 1000 ppm to about 5000 ppm relative to the batch size (i.e., the total weight). A salt of ascorbic acid, such as sodium or potassium ascorbate, is particularly preferred in this capacity. Other processing aids include, without limitation, buffering acids and/or their salts such as phosphoric acid, acetic acid, citric acid, and the like.

Structure of Microcapsules

In one embodiment, microcapsules of the invention have a structure generally as depicted in FIG. 2. FIG. 2 depicts a multi-core microcapsule prepared according to a multi-step process of the invention. Primary microcapsules comprise cores 18 (i.e. the loading substance) surrounded by first shells 20. The primary microcapsules agglomerate and the space 22 between them is usually at least partly filled by additional shell material of same composition as first shell 20, although there may be voids between some of the primary microcapsules. The agglomeration of primary microcapsules is surrounded by a second shell 24.

Multi-core microcapsules comprising second shell 24 may be prepared according to the processes described herein and exemplified in the examples or by generally the same techniques that are described in Applicant's co-pending U.S. patent application Ser. No. 10/120,621 filed Apr. 11, 2002, corresponding to International Application No. PCT/CA2003/000520 filed Apr. 8, 2003, the disclosures of both of which are incorporated herein by reference. These multi-core microcapsules are particularly useful because the foam-like structure of primary microcapsules, supported by additional shell material in space 22 and surrounded by second shell 24 is an extremely strong, rupture-resistant structure that has a high payload i.e. the ratio of the total mass of the cores to the total mass of the multi-core microcapsule is very high, e.g. at least 50, 55, 60, 65, 70, 75, 80, 85, 90% or higher. This is called a “one-step” process when shells 20 and 24 are of the same composition and formed in a single step. When shells 20 and 24 are of different composition, the process involves two steps.

Commercially available multicore microcapsules may also be used as starting materials. An example is the Driphorm™ Hi-DHA™ microencapsulated tuna oil, manufactured by Nu-Mega Ingredients Pty. Ltd., Queensland, AU.

In accordance with the invention, a three-step process takes place when a third shell 26 is formed on the multi-core microcapsule. Third shell 26 further strengthens the microcapsule and can be advantageously used to provide a shell having properties different from those of shell 24. For instance, different polymer components can be incorporated into third shell 26. In addition, or alternatively, lipids may be incorporated into shell 26 to increase moisture or oxygen impermeability or the like. These properties might instead be incorporated into second shell 24 rather than third shell 26 (or also into second shell 24 as well as into third shell 26), depending on the requirements for a particular purpose. Additional shells, not shown in FIG. 2, may be formed around third shell 26, by the methods and techniques of the invention. For instance, N additional shells could be added, wherein N is an integer from 1 to 20.

At least one of shells 20, 24 and 26 and of any additional shells comprises a complex coacervate, as described above. Preferably, at least two of the shells comprise a complex coacervate. Even more preferably, all of the shells comprise a complex coacervate. For instance, the following shells may comprise complex coacervates: (a) shell 20; (b) shell 24; (c) shell 26; (d) shells 20 and 24; (e) shells 20 and 26; (f) shells 24 and 26; or (g) shells 20, 24 and 26. Additional shells also preferably comprise a complex coacervate.

Referring again to FIG. 2, the primary microcapsules (i.e. cores 18 surrounded by first shells 20) typically have an average diameter of about 40 nm to about 10 μm, more particularly from about 0.1 μm to about 5 μm, even more particularly an average diameter of about 1-2 μm. The finished multi-core microcapsule, i.e. including third shell 26, usually has an average diameter from about 1 μm to about 2000 μm, more typically from about 20 μm to about 1000 μm, more particularly from about 20 μm to about 100 μm and even more particularly from about 50 μm to about 100 μm.

In FIG. 2, second shell 24 and third shell 26 are depicted as discrete layers. This will be the case if the shells are formed of the different shell materials. In that case, even if they do not differ in appearance, they will have a different composition and can be represented as discrete, distinct layers. But if second shell 24 and third shell 26 are formed of the same shell material, they may, as shown in FIG. 3, merge to form a single, continuous layer, having the combined thickness of second shell 24 and third shell 26. As shown in FIG. 3, when the second and third shells are of the same composition, there may be no discrete boundary separating them. This would be true also in microcapsules of the invention having fourth or additional shells that are of the same composition as the preceding shell.

The invention is also useful in the preparation of single-core microcapsules having multiple shells. Single-core microcapsules useful as starting materials are commercially available. Examples include microencapsulated flavours by Givaudan Flavors Corp., Cincinnati, Ohio, USA, and microencapsulated minerals and vitamins by Watson Food Co. Inc., West Haven, Conn., USA. Alternatively, they can be made by complex coacervation processes as described herein, e.g. by preparing primary microcapsules without a further agglomeration step. FIG. 4 depicts a single-core microcapsule having multiple shells in accordance with the invention. Core 18 is surrounded by a first shell 20 and a second shell 24. Additional shells, not shown in FIG. 4, may be formed around second shell 24, by the methods and techniques of the invention. For instance, N additional shells could be added, wherein N is an integer from 1 to 20.

As with the multi-core microcapsules, shells 20 and 24 of single-core microcapsules may be of the same or different composition. At least one of shells 20 and 24 and of any additional shells comprises complex coacervates as described above. Preferably, at least two of the shells comprise a complex coacervate. Even more preferably all of the shells comprise a complex coacervate. For instance, the following shells may comprise complex coacervates: (a) shell 20; (b) shell 24; or (c) shells 20 and 24. Additional shells also preferably comprise complex coacervates.

Single-core microcapsules may be as large as multi-core microcapsules. For instance, the exterior diameter of second shell 24 in the single-core microcapsule of FIG. 4 may be from about 1 μm to about 2000 μm. More typically it will be from about 20 μm to about 1000 μm, more particularly from about 20 μm to about 100 μm and even more particularly from about 50 μm to about 100 μm.

When they are of the same composition, first shell 20 and second shell 24 (and any additional shell) of the single-core multicapsule may merge to form a single continuous layer as depicted in FIG. 5. This may be done in a one-step process.

Processes

Single or multi-core microcapsules to which additional shells may be added by the processes of the invention may be obtained from commercial sources. In a particularly preferred embodiment, multi-core microcapsules prepared in accordance with applicant's co-pending U.S. patent application Ser. No. 10/120,621 filed Apr. 11, 2002, corresponding to International Application No. PCT/CA2003/000520 filed Apr. 8, 2003, the disclosures of both of which are incorporated herein by reference, are used. Such microcapsules can be prepared e.g. by a one step process as follows.

An aqueous mixture of a loading substance (i.e. core material) and a polymer component of the shell material is formed. The aqueous mixture may be a mechanical mixture, a suspension or an emulsion. When a liquid loading material is used, particularly a hydrophobic liquid, the aqueous mixture is preferably an emulsion of the loading material and the polymer components.

In a more preferred aspect, a first polymer component is provided in aqueous solution, preferably together with processing aids, such as antioxidants. A loading substance may then be dispersed into the aqueous mixture, for example, by using a homogenizer. If the loading substance is a hydrophobic liquid, an emulsion is formed in which a fraction of the first polymer component begins to deposit around individual droplets of loading substance to begin the formation of primary shells. If the loading substance is a solid particle, a suspension is formed in which a fraction of the first polymer component begins to deposit around individual particles to begin the formation of primary shells. At this point, another aqueous solution of a second polymer component may be added to the aqueous mixture.

Droplets or particles of the loading substance in the aqueous mixture preferably have an average diameter of less than 100 μm, more preferably less than 50 μm, even more preferably less than 25 μm. Droplets or particles of the loading substance having an average diameter less than 10 μm or less than 5 μm or less than 3 μm or less than 1 μm may be used. Particle size may be measured using any typical equipment known in the art, for example, a Coulter™ LS230 Particle Size Analyzer, Miami, Fla., USA.

The amount of the polymer components of the shell material provided in the aqueous mixture is typically sufficient to form both the primary and outer shells of microcapsules. Preferably, the loading substance is provided in an amount of from about 1% to about 15% by weight of the aqueous mixture, more preferably from about 3% to about 8% by weight, and even more preferably about 6% by weight.

If a complex coacervate is desired, the pH, temperature, concentration, mixing speed or a combination thereof is then adjusted to accelerate the formation of the primary shells of complex coacervate around the droplets or particles of the loading substance to form primary microcapsules. In the case of multicore microcapsules, agglomeration of the primary microcapsules will take place to form discrete clumps at desired size and shape.

pH is an expression of the concentration of hydrogen ions in solution. Such ions affect the ionization equilibria of the component A and B polymers involved in complex coacervation and thus the formation of complex coacervates. The pH is adjusted so that the component A polymer will bear a net positive charge and the component B polymer will bear a net negative charge. Hence, the pH adjustment depends on the type of shell material to be used.

For example, when gelatine type A is a polymer component, the gelatine molecules have nearly equal positive and negative charges (i.e. zero net polarity change) at their point of zero charge (pzc) around pH 9-10. Only when the solution pH is lower than the pzc value, will the polymer bear a net positive charge, which interacts with the negatively charged component B (e.g. gum arabic, polyphosphate, alginate, etc.).

In the case of gelatine type A, the pH is preferably adjusted to a value from 3.5-5.0, more preferably from 4.0-5.0. Much outside this range, the gelatine-based complex tends to form gels upon cooling rather than a shell on the microcapsules. If the pH of the mixture starts in the desired range, then little or no pH adjustment is required.

The molar ratio of components A and B is adjusted to favour formation of shells on the microcapsules rather than merely the formation of gel particles in solution. Suitable molar ratios are discussed above under the heading “Shell Material”.

The concentration of components A and B in the aqueous mixture may also affect the formation of complex coacervates and can be adjusted accordingly. Typically, the total concentration of components A and B varies from 1% to 20%, preferably 2-10%, and more preferably 3-6% by weight of the aqueous mixture. For instance, when gelatine type A is used as component A, the concentration of gelatine type A is preferably from 1-15% by weight of the aqueous mixture, more preferably 2-6% by weight and even more preferably 2-4% by weight. Similarly, when polyphosphate is used as component B, its concentration in the aqueous mixture is preferably 0.01-0.65% by weight of the aqueous mixture, more preferably 0.13-0.17% by weight, even more preferably 0.13-0.26% by weight.

The initial temperature of the aqueous mixture is preferably set to a value of from about 40° C. to about 60° C., more preferably at about 50° C.

Mixing speed influences the deposition of complex coacervates on the surface of microcapsules. If the mixing speed is too low, the aqueous mixture is agitated insufficiently and undesirably large microcapsules may be formed. Conversely, if the mixing speed is too high, high shear forces are generated and prevent shell material from forming on the microcapsules. Instead, gel particles form in the solution. The mixing speed is preferably between 100 and 1500 rpm, more preferably between 400 and 1000 rpm and even more preferably between 600 and 800 rpm. Particular mixing parameters depend on the type of equipment being used. Any of a variety of types of mixing equipment known in the art may be used. Particularly useful is an axial flow impeller, such as Lightnin™ A310 or A510.

At this time, materials for outer shell are added into the mixture, and the aqueous mixture may then be cooled under controlled cooling rate and mixing parameters to permit coating of the primary microcapsules to form outer shells. It is advantageous to control the formation of the outer shell at a temperature above the gel point of the shell material. It is also possible at this stage to further add more polymer components, either of the same kind or a different kind, in order to thicken the outer shell and/or produce microcapsules having different layers of shells to provide desired functionalities. The temperature is preferably lowered at a rate of about 1° C./10 minutes until it reaches a temperature of from about 5° C. to about 10° C., preferably about 5° C. The outer shell encapsulates the primary microcapsules or clumps to form a rigid encapsulated agglomeration of microcapsules.

At this stage, a cross-linker may be added to further increase the rigidity of the microcapsules by cross-linking the shell material in both the outer and primary shells and to make the shells insoluble in both aqueous and non-aqueous (e.g., oil) media. Any suitable cross-linker may be used and the choice of cross-linker depends somewhat on the choice of shell material. Preferred cross-linkers are enzymatic cross-linkers (e.g. transglutaminase), aldehydes (e.g. formaldehyde or gluteraldehyde), tannic acid, alum, organic or inorganic calcium or potassium salt, or a mixture thereof. When the microcapsules are to be used to deliver a biologically active substance to an organism, the cross-linkers are preferably non-toxic or of sufficiently low toxicity. The type and the amount of cross-linker used depend on the type of shell material and may be adjusted to provide more or less structural rigidity as desired. For example, when gelatine type A is used in the shell material, transglutaminase may be conveniently used in an amount of about 0.2% to about 2.0%, preferably about 1.0%, by weight of microcapsule suspension. In general, one skilled in the art may routinely determine the desired amount in any given case by simple experimentation.

At this stage, multi-core microcapsules have been produced. These microcapsules or other microcapsules may then be processed in accordance with the invention to add additional shell layers as described above. Preferably, additional shells are added after the formation of the outer shell of the microcapsule or before the cross-linking step. More particularly, first and second polymer components of shell material are dissolved in aqueous solution e.g. at 40 to 60° C., more preferably around 50° C. pH may be controlled or adjusted at this stage. The microcapsules previously prepared are then combined with this mixture. Alternatively, the microcapsules may be combined with an aqueous solution of the first polymer component of shell material and then a second aqueous solution of the second polymer component of shell material may be added. pH, temperature, concentration, mixing speed or a combination thereof can then be adjusted as described above so that the polymer components of shell material form a complex coacervate surrounding and coating the microcapsules with an additional shell. As discussed above, processing aids may be incorporated as may be hydrophobic materials such as oils, waxes, resins or fats. The new outer shell may be then cross-linked as described above. These additional steps of forming additional shell layers may be repeated as desired to build up a suitable number of further shells on the microcapsule.

Finally, the microcapsules may be washed with water and/or dried to provide a free-flowing powder. Drying may be accomplished by a number of methods known in the art, such as freeze drying, drying with ethanol or spray drying. Spray drying is a particularly preferred method for drying the microcapsules. Spray drying techniques are disclosed in “Spray Drying Handbook”, K. Masters, 5th edition, Longman Scientific Technical UK, 1991, the disclosure of which is hereby incorporated by reference.

Uses

The microcapsules produced by the processes of the present invention may be used to prepare liquids as free-flowing powders or compressed solids, to store a substance, to separate reactive substances, to reduce toxicity of a substance, to protect a substance against oxidation, to deliver a substance to a specified environment and/or to control the rate of release of a substance. In particular, the microcapsules may be used to deliver a biologically active substance to an organism for nutritional or medical purposes. The biologically active substance may be, for example, a nutritional supplement, a flavour, a drug and/or an enzyme. The organism is preferably a mammal, more preferably a human. Microcapsules containing the biologically active substance may be included, for example, in foods or beverages or in drug delivery systems. Use of the microcapsules of the present invention for formulating a nutritional supplement into human food is particularly preferred.

Microcapsules of the present invention have good rupture strength to help reduce or prevent breaking of the microcapsules during incorporation into food or other formulations. Furthermore, the microcapsules' shells can be formulated to be insoluble in both aqueous and non-aqueous (e.g., oil) media, and help reduce or prevent oxidation and/or deterioration of the loading substance during preparation of the microcapsules, during long-term storage, and/or during incorporation of the microcapsules into a formulation vehicle, for example, into foods, beverages, nutraceutical formulations or pharmaceutical formulations.

The invention will now be further illustrated by the following non-limiting examples.

EXAMPLES Example 1 Multicore Microcapsules Prepared by One-Step Process for Comparison (Both First and Second Shells Having the Same Composition of Gelatine and Polyphosphate)

54.5 grams gelatine 275 Bloom type A (isoelectric point of about 9) was mixed with 600 grams of deionized water containing 0.5% sodium ascorbate under agitation at 50° C. until completely dissolved. 5.45 grams of sodium polyphosphate was dissolved in 104 grams of deionized water containing 0.5% sodium ascorbate. 90 grams of a fish oil concentrate containing 30% eicosapentaenoic acid ethyl ester (EPA) and 20% docosahexaenoic acid ethyl ester (DHA) (available from Ocean Nutrition Canada Ltd.) was dispersed with 1.0% of an antioxidant (mixed natural tocopherols) into the gelatine solution with a high speed Polytron™ homogenizer at 5,500 rpm for 6 minutes. An oil-in-water emulsion was formed. The oil droplet size had a narrow distribution with an average size of about 1 μm measured by Coulter™ LS230 Particle Size Analyzer. The emulsion was diluted with 700 grams of deionized water containing 0.5% sodium ascorbate at 50° C. The sodium polyphosphate solution was then added into the emulsion and mixed with a Lightnin™ agitator at 600 rpm. The pH was then adjusted to 4.5 with a 10% aqueous acetic acid solution. During pH adjustment and the cooling step that followed pH adjustment, a coacervate formed from the gelatine and polyphosphate coated onto the oil droplets to form primary microcapsules. Cooling was carried out to above the gel point of the gelatine and polyphosphate and the primary microcapsules started to agglomerate to form lumps under agitation. Upon further cooling of the mixture, polymer remaining in the aqueous phase further coated the lumps of primary microcapsules to form an encapsulated agglomeration of microcapsules having an outer shell and having an average size of 50 μm. Once the temperature had been cooled to 5° C., 2.7 grams of 50% gluteraldehyde was added into the mixture to further strengthen the shell. The mixture was then warmed to room temperature and kept stirring for 12 hours. Finally, the microcapsule suspension was washed with water. The washed suspension was then spray dried to obtain a free-flowing powder. A payload of 62% was obtained.

Example 2 A Two-Step Process with Gelatine and Polyphosphate in Both First and Second Shells, But Having Different Compositions

Step A: 15.6 grams gelatine 275 Bloom type A (isoelectric point of about 9) was mixed with 172 grams of deionized water containing 0.5% sodium ascorbate under agitation at 50° C. until completely dissolved. 1.56 grams of sodium polyphosphate was dissolved in 29.7 grams of deionized water containing 0.5% sodium ascorbate. 69 grams of a fish oil concentrate containing 30% eicosapentaenoic acid ethyl ester (EPA) and 20% docosahexaenoic acid ethyl ester (DHA) (available from Ocean Nutrition Canada Ltd.) was dispersed with 1.0% of an antioxidant (mixed natural tocopherols) into the gelatine solution with a high speed Polytron™ homogenizer at 6,100 rpm for 4 minutes. An oil-in-water emulsion was formed. The oil droplet size had a narrow distribution with an average size of about 1 μm measured by Coulter™ LS230 Particle Size Analyzer. The emulsion was diluted with 319 grams of deionized water containing 0.5% sodium ascorbate at 50° C. The sodium polyphosphate solution was then added into the emulsion and mixed with a Lightnin™ agitator at 600 rpm. The pH was then adjusted to 4.5 with a 10% aqueous phosphoric acid solution. During pH adjustment and the cooling step that followed pH adjustment, a coacervate formed from the gelatine and polyphosphate coated onto the oil droplets to form primary microcapsules, and then the primary microcapsules started to agglomerate to form lumps under agitation. A payload of 80% was obtained at this step.

Step B: A gelatine solution was prepared by dissolving 41.8 grams of gelatine 275 Bloom type A (isoelectric point of about 9) in 460 grams of deionized water containing 0.5% sodium ascorbate under agitation at 50° C. until completely dissolved. A sodium polyphosphate solution was prepared by dissolving 4.18 grams of sodium polyphosphate in 79.5 grams of deionized water containing 0.5% sodium ascorbate. The gelatine and polyphosphate solutions were combined to form a mixture, and pH of the mixture was adjusted to 4.7 with 10% aqueous phosphoric acid.

Step C: The mixture from Step B was added to the mixture with lumps formed in step A. Cooling was carried out under agitation to cause the gelatine and polyphosphate to form coacervates and to coat the lumps formed in Step A to form an outer shell. The microcapsules thus formed had an average size of 60 μm. Once the temperature had been cooled to 5° C., 2.1 grams of 50% gluteraldehyde was added into the mixture to further strengthen the shell. The mixture was then warmed to room temperature and stirred continuously for 12 hours. Finally, the microcapsule suspension was washed with water. The washed suspension was then spray dried to obtain a free-flowing powder. A payload of 59% was obtained.

Example 3 A Two-Step Process having Gelatine and Alginate in the Second Shell

Step A: Same as Step A in Example 2.

Step B: A gelatine solution was prepared by dissolving 23.0 grams of gelatine 275 Bloom type A (isoelectric point of about 9) in 371 grams of deionized water under agitation at 50° C. until completely dissolved. A sodium alginate (ISP Alginates) solution was prepared by dissolving 3.00 grams of sodium alginate in 503.8 grams of deionized water. The gelatine and sodium alginate solutions were combined to form a mixture. The pH of the mixture was adjusted to 5.00 with 10% aqueous phosphoric acid.

Step C: The mixture from Step B was added to the mixture with lumps formed in step A. Cooling was carried out under agitation to cause gelatine and alginate to form coacervates and coat the lumps formed in Step A to form an outer shell. The microcapsules thus formed had an average size of around 80 μm. Once the temperature had been cooled to 5° C., 2.1 grams of 50% gluteraldehyde was added into the mixture to further strengthen the shell. The mixture was then warmed to room temperature and stirred continuously for 12 hours. Finally, the microcapsule suspension was washed with water. The washed suspension was then spray dried to obtain a free-flowing powder. A payload of 53% was obtained.

Example 4 A Three-Step Process to Incorporate Wax and Alginate in the Second Shell and Alginate in the Third Shell

Step A: 20.0 grams gelatine 275 Bloom type A (isoelectric point of about 9) was mixed with 220.1 grams of deionized water containing 0.5% sodium ascorbate under agitation at 50° C. until completely dissolved. 2.00 grams of sodium polyphosphate was dissolved in 38.0 grams of deionized water. 88.0 grams of a fish oil concentrate containing 30% eicosapentaenoic acid ethyl ester (EPA) and 20% docosahexaenoic acid ethyl ester (DHA) (available from Ocean Nutrition Canada Ltd.) was dispersed with 1.0% of an antioxidant (mixed natural tocopherols) into the gelatine solution with a high speed Polytron™ homogenizer at 6,100 rpm for 4 minutes. An oil-in-water emulsion was formed. The oil droplet size had a narrow distribution with an average size of about 1 μm measured by Coulter™ LS230 Particle Size Analyzer. The emulsion was diluted with 408.6 grams of deionized water at 50° C. The sodium polyphosphate solution was then added into the emulsion and mixed with a Lightnin™ agitator at 600 rpm. The pH was then adjusted to 4.5 with a 10% aqueous phosphoric acid solution. During pH adjustment and the cooling step that followed pH adjustment, a coacervate formed from the gelatine and polyphosphate coated onto the oil droplets to form primary microcapsules, and then the primary microcapsules started to agglomerate to form lumps under agitation. A payload of 80% was obtained at this step.

Step B: A gelatine solution was prepared by dissolving 8.6 grams of gelatine 275 Bloom type A (isoelectric point of about 9) in 94.5 grams of deionized water under agitation at 65° C. until completely dissolved. 25.8 grams of beeswax melted at 65° C. was emulsified in the gelatine solution with a high speed Polytron™ homogenizer at 6,100 rpm for 4 minutes. A wax-in-water emulsion was formed. An alginate solution was prepared by dissolving 2.3 grams of sodium alginate in 192 grams of deionized water was added to the emulsion, and pH of the mixture was adjusted to 4.7 with 10% aqueous phosphoric acid. The mixture was then added into lump mixtures in step A under agitation at 800 rpm, and cooling was carried out to cause the gelatine-alginate-wax composite material to form a coating onto the lumps formed in Step A to form microcapsules. A payload of 60% was obtained at this step.

Step C: A solution was prepared by dissolving 23.1 grams of gelatine and 2.3 grams of sodium alginate in 384.9 grams of deionized water under agitation at 50° C. until completely dissolved. pH of the mixture was adjusted to 4.5 with 10% aqueous phosphoric acid, and the mixture was then added into microcapsule mixtures formed in step B under agitation at 800 rpm. Cooling was carried out to cause the gelatine-alginate material to form a coating onto the microcapsules that formed in Step B. Once the temperature had been cooled to 5° C., 1.5 grams of transglutaminase was added into the mixture to cross-link the shell. The mixture was then warmed to room temperature and kept stirring for 12 hours. Finally, the microcapsule suspension was spray dried to obtain a free-flowing powder. A final payload of 52% was obtained.

Example 5 A Two-Step Process of Multicore Microcapsules Having Wax and Alginate in the Second Shell

Step A: 13.0 grams of gelatine 275 Bloom type A (isoelectric point of about 9) was mixed with 143.0 grams of deionized water containing 0.5% sodium ascorbate under agitation at 50° C. until completely dissolved. 1.3 grams of sodium polyphosphate was dissolved in 24.7 grams of deionized water. 57.2 grams of fish oil containing 18% eicosapentaenoic acid (EPA) and 12% docosahexaenoic acid (DHA) (available from Ocean Nutrition Canada Ltd.) was dispersed with 1.0% of an antioxidant (mixed natural tocopherols) into the gelatine solution with a high speed Polytron™ homogenizer at 8,000 rpm for 4 minutes. An oil-in-water emulsion was formed. The oil droplet size had a narrow distribution with an average size of about 1 μm measured by Coulter™ LS230 Particle Size Analyzer. The emulsion was diluted with 266.0 grams of deionized water at 50° C. The sodium polyphosphate solution was then added into the emulsion and mixed with a Lightnin™ agitator at 350 rpm. The pH was then adjusted to 4.4 with a 10% aqueous phosphoric acid solution. During pH adjustment and the cooling step that followed pH adjustment, a coacervate formed from the gelatine and polyphosphate coated onto the oil droplets to form primary microcapsules, and then the primary microcapsules started to agglomerate to form lumps under agitation. A payload of 80% was obtained at this step.

Step B: A gelatine solution was prepared by dissolving 7.05 grams of gelatine 275 Bloom type A (isoelectric point of about 9) in 77.9 grams of deionized water under agitation at 70° C. until completely dissolved. 7.05 grams of beeswax melted at 70° C. was emulsified in the gelatine solution with a high speed Polytron™ homogenizer at 8,000 rpm for 4 minutes. A wax-in-water emulsion was formed. An alginate solution (45° C.) was prepared by dissolving 7.62 grams of sodium alginate in 630 grams of deionized water was added to the emulsion, and pH of the mixture was adjusted to 5.3 with 10% aqueous phosphoric acid. The mixture was then added into lump mixtures in step A under agitation at 450 rpm followed by adjusting the pH value of the mixture to 4.9, and cooling was carried out to cause the gelatine-alginate-wax composite material to form a coating onto the lumps formed in Step A to form microcapsules. Once the temperature had been lowered to 5° C., 3.8 grams of transglutaminase was added into the mixture to cross-link the shells. The mixture was then warmed up to room temperature and stirred at 600 rpm for 12 hours. Finally, the microcapsule suspension was spray dried to obtain a free-flowing powder. A final payload of 57% was obtained.

Example 6 Evaluation of Microcapsules

Images of microcapsules of Examples 1-5 are shown in FIG. 6 to FIG. 10, respectively. It can be seen clearly that at approximately the same payload (60%) the microcapsules prepared with a two step process (FIG. 7) have much thicker outer shells than those prepared with one step process (FIG. 6). The microcapsules prepared with a three step process having a composite shell containing lipids (FIG. 9) clearly show the lipid droplets incorporated in the second shell and near the agglomerated oil core.

Accelerated oxidative stability in dry state was evaluated by placing the prepared microcapsule powders from each of Examples 1-4 in an oxygen bomb (Oxipres™, MIKROLAB AARHUS A/S, Denmark) with an initial oxygen pressure of 5 bar at a constant temperature of 65° C. When the encapsulated fish oil started to oxidize, the oxygen pressure dropped, and an induction period or time was determined. A longer induction period means that the contents of the microcapsules are better protected towards oxidation.

Induction periods are shown in Table 1. The microcapsules made from a two-step process in accordance with the invention have higher induction period (50-56 hours) than those made from a one-step process (41 hours). This translates to 22.0% to 37.6% increase in oxidative stability.

TABLE I
Comparison of the microcapsules described in Examples 1-5.
Loading Induction
Example # Figure # Description (%) period (hr)
1 6 Multicore one-step 62 41
process for
comparison
2 7 Two-step process 59 50
with gelatine and
polyphosphate in
outer shell
3 8 Two-step process 53 55
with alginate in
outer shell
4 9 Three-step process 52 44
incorporating wax
and alginate in
the second shell
and gelatine and
polyphosphate in
the third shell
5 10 Two-step process 57 56
incorporating wax
and alginate in
the shell

All publications cited in this specification are herein incorporated by reference as if each individual publication were specifically and individually indicated to be incorporated by reference. The citation of any publication should not be construed as an admission that such publication is prior art.

Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this specification that certain changes or modifications may be made thereto without departing from the spirit or scope of the appended claims.

Claims (11)

The invention claimed is:
1. A microcapsule consisting essentially of:
(a) an agglomeration of primary microcapsules, each primary microcapsule comprising a loading substance and a first shell surrounding the loading substance;
(b) a second shell surrounding said agglomeration; and
(c) a third shell surrounding said second shell;
wherein the first shell and second shell are formed from a complex coacervate between gelatin A and polyphosphate and the third shell is formed from a different complex coacervate, wherein the loading substance comprises at least 50% of the total mass of the microcapsule, and wherein the third shell comprises an antioxidant.
2. The microcapsule according to claim 1, wherein the third shell is formed from a complex coacervates comprising at least one polymer component selected from the group consisting of: a protein, a polyphosphate, a polysaccharide, gum arabic, alginate, chitosan, carrageenan, pectin, cellulose and cellulose derivatives.
3. The microcapsule according to claim 2, wherein the protein is selected from the group consisting of gelatine type A, gelatine type B, soy protein, whey protein, milk protein, and combinations thereof.
4. The microcapsule according to claim 1, further comprising at least one additional shell surrounding said third shell.
5. The microcapsule according to claim 4, wherein said at least one additional shell surrounding said third shell comprises is formed from a complex coacervate.
6. The microcapsule according to claim 1, wherein the second shell comprises an antioxidant.
7. The microcapsule according to claim 1, wherein at least one of the second and third shells comprises one or more hydrophobic components selected from the group consisting of waxes, oils, resins, and fats.
8. The microcapsule according to claim 1, wherein the third shell is cross-linked with an enzymatic cross-linker.
9. The microcapsule according to claim 1, having an exterior average diameter of from about 1 μm to about 2000 μm, and wherein said first shells have an average diameter of from about 40 nm to about 10 μm.
10. The microcapsule according to claim 1, wherein the loading substance comprises an omega-3 fatty acid, a derivative thereof, or mixture thereof.
11. The microcapsule according to claim 4, wherein at least one additional shell comprises one or more hydrophobic components selected from the group consisting of waxes, oils, resins, and fats.
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Families Citing this family (91)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4944348B2 (en) * 2000-09-08 2012-05-30 三栄源エフ・エフ・アイ株式会社 Tetraphenyl bacteriochlorin derivatives and compositions comprising the same
US6974592B2 (en) * 2002-04-11 2005-12-13 Ocean Nutrition Canada Limited Encapsulated agglomeration of microcapsules and method for the preparation thereof
WO2004041251A1 (en) 2002-11-04 2004-05-21 Ocean Nutrition Canada Limited Microcapsules having multiple shells and method for the preparation thereof
WO2005018333A1 (en) * 2003-08-22 2005-03-03 Danisco A/S Composition comprising a bacteriocin and an extract from a plant of the labiatae family
JP4926707B2 (en) * 2003-08-22 2012-05-09 ダニスコ エイ/エス Encapsulated antimicrobial material
GB0319817D0 (en) 2003-08-22 2003-09-24 Danisco Microcapsules method for preparing same and use thereof
ES2235642B2 (en) * 2003-12-18 2006-03-01 Gat Formulation Gmbh Process continuous multi-microencapsulation to improve the stability and storage of biologically active ingredients.
US6969530B1 (en) 2005-01-21 2005-11-29 Ocean Nutrition Canada Ltd. Microcapsules and emulsions containing low bloom gelatin and methods of making and using thereof
US8034450B2 (en) * 2005-01-21 2011-10-11 Ocean Nutrition Canada Limited Microcapsules and emulsions containing low bloom gelatin and methods of making and using thereof
WO2006109194A3 (en) * 2005-01-27 2006-12-07 Colin James Barrow Chromium-fatty acid compounds and methods of making and using thereof
EP3238543A1 (en) 2005-06-07 2017-11-01 DSM Nutritional Products AG Eukaryotic microorganisms for producing lipids and antioxidants
US20090274791A1 (en) * 2005-07-07 2009-11-05 Mattson Pete H Food Articles With Delivery Devices and Methods for the Preparation Thereof
CN104473161A (en) * 2005-07-07 2015-04-01 帝斯曼营养品股份公司 Food articles with delivery devices and methods for the preparation thereof
US7977498B2 (en) 2005-08-26 2011-07-12 Ocean Nutrition Canada Limited Reduction of sterols and other compounds from oils
WO2007088421A3 (en) 2005-08-26 2008-01-03 Ocean Nutrition Canada Ltd A process for the removal of sterols and other compounds from glycerol oils
CA2620507C (en) * 2005-08-30 2011-07-19 Firmenich Sa Encapsulated active ingredients, methods of preparation and their use
KR20080059175A (en) * 2005-09-07 2008-06-26 사우스웨스트 리서치 인스티튜트 Biodegradable microparticle pharmaceutical formulations exhibiting improved release rates
US9693967B2 (en) 2005-09-07 2017-07-04 Southwest Research Institute Biodegradable microparticle pharmaceutical formulations exhibiting improved released rates
US7614812B2 (en) * 2005-09-29 2009-11-10 Kimberly-Clark Worldwide, Inc. Wiper with encapsulated agent
US7485609B2 (en) * 2005-09-29 2009-02-03 Kimberly-Clark Worldwide, Inc. Encapsulated liquid cleanser
US7678399B2 (en) 2005-12-05 2010-03-16 Bunge Oils, Inc. Phytosterol containing deep-fried foods and methods with health promoting characteristics
US7914891B2 (en) * 2005-12-28 2011-03-29 Kimberly-Clark Worldwide, Inc. Wipes including microencapsulated delivery vehicles and phase change materials
US20070149435A1 (en) * 2005-12-28 2007-06-28 Kimberly-Clark Worldwide, Inc. Cleansing composition including microencapsulated delivery vehicles
US20070148446A1 (en) * 2005-12-28 2007-06-28 Kimberly-Clark Worldwide, Inc. Wipes including microencapsulated delivery vehicles and processes of producing the same
US20070145618A1 (en) * 2005-12-28 2007-06-28 Kimberly-Clark Worldwide, Inc. Methods of making microencapsulated delivery vehicles
US7442439B2 (en) * 2005-12-28 2008-10-28 Kimberly-Clark Worldwide, Inc. Microencapsulated heat delivery vehicles
US20070148448A1 (en) * 2005-12-28 2007-06-28 Kimberly-Clark Worldwide, Inc. Microencapsulated delivery vehicles including cooling agents
US20070145619A1 (en) * 2005-12-28 2007-06-28 Kimberly-Clark Worldwide, Inc. Processes for producing microencapsulated delivery vehicles
US20070202185A1 (en) * 2005-12-28 2007-08-30 Kimberly-Clark Worldwide, Inc. Microencapsulated Delivery Vehicles Having Fugitive Layers
US20070148459A1 (en) * 2005-12-28 2007-06-28 Kimberly-Clark Worldwide, Inc. Microencapsulated delivery vehicles
JP2009533490A (en) 2006-04-07 2009-09-17 オーシャン ニュートリッション カナダ リミテッド Emulsions and microcapsules containing a substance having a low interfacial tension and methods of making and using them,
US7654412B2 (en) * 2006-05-30 2010-02-02 Kimberly-Clark Worldwide, Inc. Wet wipe dispensing system for dispensing warm wet wipes
US7497351B2 (en) 2006-05-30 2009-03-03 Kimberly-Clark Worldwide, Inc. Wet wipe dispensing system
US7648046B2 (en) * 2006-05-30 2010-01-19 Kimberly-Clark Worldwide, Inc. Dispensing system for dispensing warm wet wipes
EP2040682B1 (en) * 2006-06-05 2017-07-26 DSM Nutritional Products AG Microcapsules with improved shells
US8221809B2 (en) 2006-06-22 2012-07-17 Martek Biosciences Corporation Encapsulated labile compound compositions and methods of making the same
CN105154481A (en) 2006-08-01 2015-12-16 帝斯曼营养品股份公司 Oil producing microbes and methods of modification thereof
US9032971B2 (en) 2006-11-15 2015-05-19 Philip Morris Usa Inc. Moist tobacco product and method of making
US8192841B2 (en) * 2006-12-14 2012-06-05 Kimberly-Clark Worldwide, Inc. Microencapsulated delivery vehicle having an aqueous core
WO2008085997A3 (en) 2007-01-10 2008-09-12 Ocean Nutrition Canada Ltd Vegetarian microcapsules
EP2120603A1 (en) * 2007-02-13 2009-11-25 S-Biotek Holding ApS Diet product comprising alginate
US8356606B2 (en) * 2007-06-01 2013-01-22 Philip Morris Usa Inc. Production of micronized encapsulated tobacco particles for tobacco flavor delivery from an oral pouch
WO2009004488A3 (en) 2007-06-08 2010-01-21 Philip Morris Products S.A. Capsule clusters for oral consumption
US20090004233A1 (en) * 2007-06-19 2009-01-01 Connolly Brian J Microencapsulating compositions, methods of making, methods of using and products thereof
US9332774B2 (en) * 2007-06-27 2016-05-10 Bunge Oils, Inc. Microencapsulated oil product and method of making same
WO2009016091A1 (en) * 2007-08-01 2009-02-05 Unilever Plc Coated particles
US8312886B2 (en) * 2007-08-09 2012-11-20 Philip Morris Usa Inc. Oral tobacco product having a hydrated membrane coating and a high surface area
US9186640B2 (en) * 2007-08-28 2015-11-17 Pepsico, Inc. Delivery and controlled release of encapsulated lipophilic nutrients
US20100272859A1 (en) * 2007-08-28 2010-10-28 Pepsico, Inc. Delivery and controlled release of encapsulated water-insoluble flavorants
US8469037B2 (en) 2008-02-08 2013-06-25 Philip Morris Usa Inc. Pre-portioned moist product and method of making
US7924142B2 (en) * 2008-06-30 2011-04-12 Kimberly-Clark Worldwide, Inc. Patterned self-warming wipe substrates
US20100028503A1 (en) * 2008-07-30 2010-02-04 Jimbay Peter Loh Simultaneous Multiple Acervation Process
US8551517B2 (en) 2008-12-16 2013-10-08 Kimberly-Clark Worldwide, Inc. Substrates providing multiple releases of active agents
US8778867B2 (en) 2008-12-18 2014-07-15 Firmenich Sa Microcapsules and uses thereof
CN102300473A (en) * 2009-01-30 2011-12-28 荷兰联合利华有限公司 Oil in water emulsions
US9167847B2 (en) * 2009-10-09 2015-10-27 Philip Morris Usa Inc. Production of coated tobacco particles suitable for usage in a smokeless tobacoo product
US9687023B2 (en) * 2009-10-09 2017-06-27 Philip Morris Usa Inc. Moist smokeless tobacco product for oral usage having on a portion of the outer surface at least one friction reducing strip that provides texture during use
JP5560017B2 (en) * 2009-10-13 2014-07-23 旭化成ケミカルズ株式会社 Fatty, tablets and their preparation containing multi-core microcapsules containing a triglyceride or a mixture thereof
US8539958B2 (en) 2009-10-13 2013-09-24 Philip Morris Usa Inc. Oral moist smokeless tobacco products with net-structured gel coating and methods of making
US8663671B2 (en) 2009-11-05 2014-03-04 Philip Morris Usa Inc. Methods and compositions for producing hydrogel capsules coated for low permeability and physical integrity
US9226524B2 (en) 2010-03-26 2016-01-05 Philip Morris Usa Inc. Biopolymer foams as filters for smoking articles
US9259030B2 (en) * 2010-03-26 2016-02-16 Philip Morris Usa Inc. Fabrication of core/shell capsules of different geometries and treatment thereafter
KR20130008564A (en) * 2010-03-26 2013-01-22 필립모리스 프로덕츠 에스.에이. Solid flavor encapsulation by applying complex coacervation and gelation technology
US8915255B2 (en) 2010-03-26 2014-12-23 Philip Morris Usa Inc. Smoking article with heat resistant sheet material
WO2011126165A1 (en) * 2010-04-09 2011-10-13 주식회사 포스코 Organic corrosion inhibitor-embedded polymer capsule, preparation method thereof, composition containing same, and surface treated steel sheet using same
EP2629913A4 (en) * 2010-09-20 2015-09-30 Spi Pharma Inc Microencapsulation process and product
FR2969907B1 (en) * 2010-12-31 2014-03-07 Capsum capsules series comprising at least one drop of internal phase in a drop of intermediate phase and manufacturing METHOD
CN102526124B (en) * 2011-01-31 2013-11-20 成都科尔医药技术有限公司 Traditional Chinese medicinal powder and preparation method thereof
DE102011018716A1 (en) * 2011-04-26 2012-10-31 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Microcapsule useful for micro-encapsulation, comprises an outer sheath and a volume of an antifreeze agent, which is enclosed by the outer sheath
US20130004617A1 (en) * 2011-07-01 2013-01-03 Pepsico, Inc. Coacervate complexes, methods and food products
CN102977857B (en) * 2011-09-06 2015-12-09 比亚迪股份有限公司 A phase change thermal energy storage and preparation method of microcapsules
CN103857465B (en) * 2011-09-13 2017-07-28 理研维他命股份有限公司 The method of manufacturing a multicore gelatin microcapsule
US20130095210A1 (en) * 2011-10-13 2013-04-18 Pepsico, Inc. Complex Coacervates and Aqueous Dispersions of Complex Coacervates and Methods of Making Same
ES2610968T3 (en) 2012-05-21 2017-05-04 Dsm Nutritional Products Ag Compositions and methods for increasing the stability of additives for food products
US8617610B2 (en) 2012-05-21 2013-12-31 Dsm Nutritional Products Ag Compositions and methods for increasing the stability of food product additives
GB201210156D0 (en) * 2012-06-08 2012-07-25 Imerys Minerals Ltd Microcapsules
WO2014022505A1 (en) 2012-07-31 2014-02-06 Dsm Nutritional Products Ag Refinement of oils using green tea extract antioxidants
US20150250689A1 (en) * 2012-09-24 2015-09-10 Firmenich Sa Multilayered core/shell microcapsules
KR20140042672A (en) * 2012-09-28 2014-04-07 (주)아모레퍼시픽 Microcapsule containing glycoprotein of plant origin
FR2996418B1 (en) * 2012-10-09 2015-05-29 Seppic Sa food compositions comprising capsules obtained by coacervation not implementing toxic CROSSLINKER
FR2996466B1 (en) * 2012-10-09 2015-06-05 Seppic Sa Method of encapsulation by coacervation not implementing toxic CROSSLINKER
KR101362800B1 (en) * 2012-10-16 2014-02-14 한국식품연구원 Prolamine-positive ion complex contaning phytosterol and method thereof
WO2014084423A1 (en) * 2012-11-30 2014-06-05 (주)케이피티 Pressure sensitive destructible microcapsule containing scrubbing agents, preparation method therefor, and use therefor
WO2014141098A1 (en) 2013-03-13 2014-09-18 Dsm Nutritional Products Ag Engineering microorganisms
KR101691644B1 (en) * 2013-12-04 2017-01-03 주식회사 씨앤지 The functional material containing the Polymeric microcapsules and its manufacturing method
CN103769020B (en) * 2014-01-21 2016-03-02 华南理工大学 A dual-core microcapsule and its preparation method and application
US9528983B2 (en) * 2014-05-12 2016-12-27 Anna Merritt Holmes Physicochemical modification and application of alginate gels for the controlled release of reagents in classical solution assays and microfluidic assays
FR3031914A1 (en) * 2015-01-27 2016-07-29 Jerome Bibette Encapsulation Method
CN105286011A (en) * 2015-09-18 2016-02-03 华南理工大学 Soluble soybean polysaccharide-soybean protein-curcumin compound as well as preparation and application
KR101722067B1 (en) * 2016-01-18 2017-04-07 주식회사 씨앤지 The functional material containing the Polymeric microcapsules and its manufacturing method
CN107183767A (en) * 2017-06-08 2017-09-22 北京工商大学 Single-core edible oil and fat microcapsules and preparation method thereof

Citations (135)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2800458A (en) 1953-06-30 1957-07-23 Ncr Co Oil-containing microscopic capsules and method of making them
US2800457A (en) 1953-06-30 1957-07-23 Ncr Co Oil-containing microscopic capsules and method of making them
DE1035319B (en) 1952-05-07 1958-07-31 Hoffmann La Roche A process for the preparation of a vitamin-containing powder
US3041289A (en) * 1959-01-02 1962-06-26 Ncr Co Method of making walled clusters of capsules
US3179600A (en) 1960-03-10 1965-04-20 Ncr Co Minute color-forming capsules and record material provided with such
US3190837A (en) 1958-12-31 1965-06-22 Ncr Co Making individual capsules by dual deposition
GB1198412A (en) 1968-01-29 1970-07-15 Ncr Co Microencapsulation Process
US3526682A (en) 1966-08-23 1970-09-01 Pfizer & Co C Microencapsulation of pharmaceuticals
US3697437A (en) 1970-05-27 1972-10-10 Ncr Co Encapsulation process by complex coacervation using inorganic polyphosphates and organic hydrophilic polymeric material
US4010038A (en) 1974-04-10 1977-03-01 Kanzaki Paper Manufacturing Co., Ltd. Process for producing microcapsules
US4217370A (en) 1977-08-25 1980-08-12 Blue Wing Corporation Lipid-containing feed supplements and foodstuffs
US4219439A (en) 1977-01-28 1980-08-26 Kanzaki Paper Manufacturing Co., Ltd. Method of making oil-containing microcapsules
US4222891A (en) 1977-08-17 1980-09-16 Kanzaki Paper Mfg. Co., Ltd. Method of making oil-containing microcapsules
US4232084A (en) 1978-01-25 1980-11-04 Thalatta, Inc. Sheets containing microencapsulated color-coded micromagnets
US4273672A (en) 1971-08-23 1981-06-16 Champion International Corporation Microencapsulation process
GB2115768A (en) 1982-02-11 1983-09-14 Kms Fusion Inc Containment of hazardous fluids
JPS58149645U (en) 1982-03-31 1983-10-07
US4442051A (en) 1980-04-21 1984-04-10 Nicholas Proprietary Limited Encapsulation of indomethacin
US4485172A (en) 1981-01-19 1984-11-27 Cpc International Inc. Multistage process for the preparation of fats and oils
GB2091286B (en) 1981-01-19 1985-06-12 Cpc International Inc Preparation of fats and oils
JPS61172807U (en) 1985-04-18 1986-10-27
US4670247A (en) 1983-07-05 1987-06-02 Hoffman-Laroche Inc. Process for preparing fat-soluble vitamin active beadlets
US4695466A (en) 1983-01-17 1987-09-22 Morishita Jintan Co., Ltd. Multiple soft capsules and production thereof
US4744933A (en) 1984-02-15 1988-05-17 Massachusetts Institute Of Technology Process for encapsulation and encapsulated active material system
US4749620A (en) 1984-02-15 1988-06-07 Massachusetts Institute Of Technology Encapsulated active material system
EP0301777A1 (en) 1987-07-28 1989-02-01 Queen's University At Kingston Multiple membrane microencapsulation
US4808408A (en) 1983-05-11 1989-02-28 Bend Research, Inc. Microcapsules prepared by coacervation
US4861627A (en) 1987-05-01 1989-08-29 Massachusetts Institute Of Technology Preparation of multiwall polymeric microcapsules
US4867986A (en) 1987-07-17 1989-09-19 Pharmachem Laboratories, Inc. Dry stabilized microemulsified omega-three acid-containing oils
US4891172A (en) 1979-10-15 1990-01-02 Mitsubishi Paper Mills, Ltd. Process for producing double-capsules
US4895725A (en) 1987-08-24 1990-01-23 Clinical Technologies Associates, Inc. Microencapsulation of fish oil
US4923855A (en) 1983-07-08 1990-05-08 The William Seroy Group Synthetic GTF chromium material and process therefor
JPH0286743U (en) 1988-12-22 1990-07-10
US4946624A (en) * 1989-02-27 1990-08-07 The Procter & Gamble Company Microcapsules containing hydrophobic liquid core
US4954492A (en) 1983-07-08 1990-09-04 The William Seroy Group Synthetic GTF chromium material for decreasing blood lipid levels and process therefor
US4963367A (en) 1984-04-27 1990-10-16 Medaphore, Inc. Drug delivery compositions and methods
US5013569A (en) 1990-05-21 1991-05-07 Century Laboratories, Inc. Infant formula
WO1991006287A1 (en) 1989-11-06 1991-05-16 Enzytech, Inc. Protein microspheres and methods of using them
EP0416575A3 (en) 1989-09-05 1991-07-24 Medaphore Inc. Drug delivery compositions based on biological materials and methods for preparing such compositions
US5035896A (en) 1988-06-15 1991-07-30 Warner-Lambert Company Water insoluble drugs coated by coacervated fish gelatin
US5051304A (en) 1986-12-18 1991-09-24 Societe Anonyme: Mero Rousselot Satia Microcapsules based on gelatin and polysaccharides and process for obtaining same
US5059622A (en) 1989-08-29 1991-10-22 Biosyn, Inc. Method for reducing blood pressure levels in hypertensive persons
WO1992011083A1 (en) 1987-09-28 1992-07-09 Redding Bruce K Jr Apparatus and method for making microcapsules
US5130061A (en) 1987-05-28 1992-07-14 Innova Di Ridolfi Flora & C. S.A.S. Process for the extraction of polyunsaturated fatty acid esters from fish oils
US5156956A (en) 1987-03-04 1992-10-20 Ajinomoto Co., Inc. Transgultaminase
US5194615A (en) 1983-07-08 1993-03-16 The William Seroy Group Synthetic GTF chromium nicotinate material and its preparation
US5204029A (en) 1989-09-25 1993-04-20 Morgan Food Products, Inc. Methods of encapsulating liquids in fatty matrices, and products thereof
EP0426428B1 (en) 1989-10-31 1993-08-11 Warner-Lambert Company Encapsulated sweetener-flavour delivery system, and its production
EP0434760B1 (en) 1988-09-19 1994-01-12 Opta Food Ingredients, Inc. Hydrophobic protein microparticles and preparation thereof
US5330778A (en) 1988-09-19 1994-07-19 Opta Food Ingredients, Inc. Hydrophobic protein microparticles
US5356636A (en) 1991-12-14 1994-10-18 Basf Aktiengesellschaft Stable vitamin and/or carotenoid products in powder form, and the preparation thereof
US5378413A (en) 1993-01-21 1995-01-03 The United States Of America As Represented By The Secretary Of The Navy Process for preparing microcapsules having gelatin walls crosslinked with quinone
US5428014A (en) 1993-08-13 1995-06-27 Zymogenetics, Inc. Transglutaminase cross-linkable polypeptides and methods relating thereto
US5456985A (en) 1990-06-13 1995-10-10 Zgoulli; Slim Microcapsules of oily liquid
US5573934A (en) 1992-04-20 1996-11-12 Board Of Regents, The University Of Texas System Gels for encapsulation of biological materials
US5603961A (en) 1992-10-01 1997-02-18 Tanabe Seiyaku Co., Ltd. Sustained release multi-core microsphere preparation and method for producing the same
US5603952A (en) 1994-12-30 1997-02-18 Tastemaker Method of encapsulating food or flavor particles using warm water fish gelatin, and capsules produced therefrom
WO1997013416A1 (en) 1995-10-12 1997-04-17 Mccormick & Company, Inc. Double encapsulation process and flavorant compositions prepared thereby
US5670209A (en) 1995-04-24 1997-09-23 Brite-Line Technologies, Inc. High brightness durable retro-reflecting microspheres and method of making the same
WO1997040701A1 (en) 1996-05-01 1997-11-06 Zymogenetics, Inc. Cross-linked protein gels and methods of making them
US5700397A (en) 1992-06-16 1997-12-23 Fuji Oil Co., Ltd. Emulsifier, emulsion composition, and powder composition
US5759599A (en) 1992-03-30 1998-06-02 Givaudan Roure Flavors Corporation Method of flavoring and mechanically processing foods with polymer encapsulated flavor oils
US5766637A (en) 1996-10-08 1998-06-16 University Of Delaware Microencapsulation process using supercritical fluids
US5780056A (en) 1996-05-10 1998-07-14 Lion Corporation Microcapsules of the multi-core structure containing natural carotenoid
US5788991A (en) 1993-04-01 1998-08-04 Novartis Corporation Coated microparticle agglomerates
US5827531A (en) 1994-12-02 1998-10-27 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Microcapsules and methods for making
US5855826A (en) 1996-09-17 1999-01-05 Pacific Corporation Matrix-double encapsulation method and a cosmetic composition containing matrix-double capsules
US5872140A (en) 1993-07-23 1999-02-16 Research Institute For Medicine And Chemistry, Inc. Vitamin D analogues
CA2318539A1 (en) 1998-01-17 1999-07-22 Henkel Kommanditgesellschaft Auf Aktien Lipoprotein creams
US5993851A (en) 1993-07-28 1999-11-30 Pharmaderm Laboratories, Ltd. Method for preparing biphasic multilamellar lipid vesicles
US5997863A (en) 1994-07-08 1999-12-07 Ibex Technologies R And D, Inc. Attenuation of wound healing processes
US6020200A (en) 1995-03-03 2000-02-01 Metabolex, Inc. Encapsulation compositions and methods
US6019998A (en) 1993-05-18 2000-02-01 Canon Kabushiki Kaisha Membrane structure
US6039901A (en) 1997-01-31 2000-03-21 Givaudan Roure Flavors Corporation Enzymatically protein encapsulating oil particles by complex coacervation
US6063820A (en) 1997-03-20 2000-05-16 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Medical food for diabetics
US6103378A (en) 1998-11-23 2000-08-15 The Mead Company Capsules having discrete solvent/color former and diluent capsule encapsulated phases
US6106875A (en) 1997-10-08 2000-08-22 Givaudan Roure (International) Sa Method of encapsulating flavors and fragrances by controlled water transport into microcapsules
US6221401B1 (en) 1996-12-02 2001-04-24 The Regents Of The University Of California Bilayer structure which encapsulates multiple containment units and uses thereof
US6234464B1 (en) 1998-07-08 2001-05-22 K.D. Pharma Bexbech Gmbh Microencapsulated unsaturated fatty acid or fatty acid compound or mixture of fatty acids and/fatty acid compounds
EP1116516A1 (en) 2000-01-13 2001-07-18 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Templating of solid particles by polymer multilayers
EP0782833B1 (en) 1996-01-05 2001-08-01 bautex Adolf Stöver Söhne KG Drawing device for a curtain
US6274174B1 (en) 1997-10-31 2001-08-14 Nisshinbo Industries, Inc. Aggregates of spherical multivalent metal alginate microparticles and methods of making them
EP0821881B1 (en) 1996-08-01 2001-09-19 Ajinomoto Co., Inc. Milk whey protein-containing powder and processed food obtained by using the same
US6300377B1 (en) 2001-02-22 2001-10-09 Raj K. Chopra Coenzyme Q products exhibiting high dissolution qualities
WO2001080656A1 (en) 2000-04-26 2001-11-01 Skånemejerier Ek.För. Lipid composition and use thereof
US6328995B1 (en) 1999-09-24 2001-12-11 Basf Aktiengesellschaft Stable vitamin and/or carotenoid products in powder form and process for their production
JP2002028473A (en) 2000-07-18 2002-01-29 Nippon Capsule Products:Kk Method for manufacturing microcapsule film of which is made airtight
US20020031553A1 (en) 2000-05-03 2002-03-14 Nora Moyano Manufacturing process of microcapsules for sustained release of water soluble peptides
US6365176B1 (en) 2000-08-08 2002-04-02 Functional Foods, Inc. Nutritional supplement for patients with type 2 diabetes mellitus for lipodystrophy
US6417233B1 (en) 1998-10-21 2002-07-09 Sigma-Tau Healthscience S.P.A. Ubiguinone-containing composition suitable for promoting enhanced intramitochondrial transportation of ubiguinones and methods of using same
US6441050B1 (en) 2000-08-29 2002-08-27 Raj K. Chopra Palatable oral coenzyme Q liquid
US6482433B1 (en) 1999-06-30 2002-11-19 Givaudan Sa Encapsulation of active ingredients
WO2002096408A1 (en) 2001-05-30 2002-12-05 Laxdale Limited Coenzyme q and eicosapentaenoic acid (epa)
US6500463B1 (en) 1999-10-01 2002-12-31 General Mills, Inc. Encapsulation of sensitive components into a matrix to obtain discrete shelf-stable particles
EP0982038B1 (en) 1998-08-24 2003-01-08 N-Zyme BioTec GmbH Stable powdery vitamin and carotenoide containing compositions and process to prepare them
US6528165B2 (en) 1999-08-17 2003-03-04 Luminex Corporation Encapsulation of discrete quanta of fluorescent particles
US20030044380A1 (en) 2001-07-19 2003-03-06 Zhu Yong Hua Adhesive including medicament
US6534926B1 (en) 2000-04-12 2003-03-18 Tmc Enterprises, A Division Of Tasco Industries, Inc. Portable fluorescent drop-light
US6534091B1 (en) 1999-07-02 2003-03-18 Cognis Iberia S. L. Microcapsules
US6544926B1 (en) 2001-10-11 2003-04-08 Appleton Papers Inc. Microcapsules having improved printing and efficiency
US20030078617A1 (en) 2001-07-16 2003-04-24 Schwartz Herbert E. Unitary surgical device and method
US20030091654A1 (en) 2000-09-21 2003-05-15 Katz David P. Methods for the treatment of diabetes, the reduction of body fat, improvement of insulin sensitivity, reduction of hyperglycemia, and reduction of hypercholesterolemia with chromium complexes, conjugated fatty acids, and/or conjugated fatty alcohols
US20030133886A1 (en) 2001-11-15 2003-07-17 Xerox Corporation Photoprotective and lightfastness-enhancing siloxanes
US6630157B1 (en) 1997-07-22 2003-10-07 Viatris Gmbh & Co. Kg. Therapeutic and dietary compositions containing essential fatty acids and bioactive disulphides
US20030193102A1 (en) * 2002-04-11 2003-10-16 Nianxi Yan Encapsulated agglomeration of microcapsules and method for the preparation thereof
US6652891B2 (en) 2001-12-12 2003-11-25 Herbasway Laboratories, Llc Co-enzyme Q10 dietary supplement
WO2003106014A1 (en) 2002-06-14 2003-12-24 Nizo Food Research B.V. Complex coacervates containing whey proteins
WO2003105606A1 (en) 2002-06-18 2003-12-24 Martek Biosciences Corporation Stable emulsions of oils in aqueous solutions and methods for producing same
WO2004041251A1 (en) 2002-11-04 2004-05-21 Ocean Nutrition Canada Limited Microcapsules having multiple shells and method for the preparation thereof
US20040106591A1 (en) 2002-11-22 2004-06-03 Pacioretty Linda M. Compositions and methods for the treatment of HIV-associated fat maldistribution and hyperlipidemia
EP1430947A1 (en) 2002-12-21 2004-06-23 Cognis Iberia, S.L. Multicompartment microparticles with liquid crystalline cores
EP0745670B1 (en) 1994-10-11 2004-06-23 Ajinomoto Co., Inc. Stabilized transglutaminase and enzymatic preparation containing the same
EP1237423B1 (en) 1999-11-18 2004-08-04 Quest International B.V. Stable, spray-dried composition in a carbohydrate substrate and process for obtaining said composition
EP0897970B1 (en) 1997-08-22 2004-09-29 Unilever N.V. Process for the production of stanol esters
US20050118285A1 (en) 2003-10-23 2005-06-02 L'oreal O/W emulsion containing aloe vera, uses thereof, method for making
WO2004054702A8 (en) 2002-12-18 2005-10-06 Lever Hindustan Ltd Complex coacervate encapsulate comprising lipophilic core
US20050249952A1 (en) * 2002-09-04 2005-11-10 Southwest Research Institute Microencapsulation of oxygen or water sensitive materials
US6969530B1 (en) 2005-01-21 2005-11-29 Ocean Nutrition Canada Ltd. Microcapsules and emulsions containing low bloom gelatin and methods of making and using thereof
US6972592B2 (en) 2003-11-24 2005-12-06 Lsi Logic Corporation Self-timed scan circuit for ASIC fault testing
JP2005522313T5 (en) 2006-03-30
EP0644771B2 (en) 1992-06-11 2006-12-06 Alkermes Controlled Therapeutics, Inc. Erythropoietin drug delivery system
US20070027028A1 (en) 2003-08-14 2007-02-01 Pears David A Microencapsulated catalyst-ligand system, methods of preparation and methods of use thereof
US20070059340A1 (en) 2005-09-09 2007-03-15 Anthony Bello Omega-3 Fatty Acids Encapsulated In Zein Coatings and Food Products Incorporating the Same
US20070078071A1 (en) 2005-09-30 2007-04-05 Kaiping Lee Spray dry capsule products and methods for preparing and using same
WO2007054207A1 (en) 2005-11-14 2007-05-18 Unilever N.V. Sterilised nutritional beverage
WO2007055815A1 (en) 2005-10-31 2007-05-18 General Mills, Inc. Encapsulation of readily oxidizable components
US20070141211A1 (en) 2005-12-16 2007-06-21 Solae, Llc Encapsulated Phospholipid-Stabilized Oxidizable Material
US20070224216A1 (en) 2004-05-04 2007-09-27 Jane Teas Methods and Compositions Related to Antiviral Therapy Using Algae and Cyanobacteria
US20090274791A1 (en) 2005-07-07 2009-11-05 Mattson Pete H Food Articles With Delivery Devices and Methods for the Preparation Thereof
US20100055281A1 (en) 2006-04-07 2010-03-04 Ocean Nutrition Canada Limited Emulsions and Microcapsules With Substances Having Low Interfacial Tension, Methods of Making and Using Thereof
US20100173002A1 (en) 2006-06-05 2010-07-08 Jin Yulai Microcapsules with improved shells
US8039030B2 (en) 2005-07-01 2011-10-18 Martek Biosciences Corporation Microwaveable popcorn and methods of making
JP5292899B2 (en) 2008-04-02 2013-09-18 セイコーエプソン株式会社 Fluid ejection device
JP5394273B2 (en) 2010-02-03 2014-01-22 本田技研工業株式会社 Hydrogen absorption material and a manufacturing method thereof
JP5828234B2 (en) 2011-06-29 2015-12-02 株式会社寺岡精工 Empty container collection device

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4749920A (en) * 1986-02-04 1988-06-07 Zinser Textilmaschinen Gmbh Multiple polyphase motor drive system for textile machine
FR2623583B2 (en) * 1987-06-23 1990-04-20 Hutchinson elastic supports
JP2000244593A (en) * 1999-02-22 2000-09-08 Sony Corp Reception equipment
JP2008015275A (en) * 2006-07-06 2008-01-24 Fuji Xerox Co Ltd Electrophotographic photoreceptor, image forming apparatus and process cartridge

Patent Citations (146)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005522313T5 (en) 2006-03-30
DE1035319B (en) 1952-05-07 1958-07-31 Hoffmann La Roche A process for the preparation of a vitamin-containing powder
US2800457A (en) 1953-06-30 1957-07-23 Ncr Co Oil-containing microscopic capsules and method of making them
US2800458A (en) 1953-06-30 1957-07-23 Ncr Co Oil-containing microscopic capsules and method of making them
US3190837A (en) 1958-12-31 1965-06-22 Ncr Co Making individual capsules by dual deposition
US3041289A (en) * 1959-01-02 1962-06-26 Ncr Co Method of making walled clusters of capsules
US3179600A (en) 1960-03-10 1965-04-20 Ncr Co Minute color-forming capsules and record material provided with such
US3526682A (en) 1966-08-23 1970-09-01 Pfizer & Co C Microencapsulation of pharmaceuticals
GB1198412A (en) 1968-01-29 1970-07-15 Ncr Co Microencapsulation Process
US3697437A (en) 1970-05-27 1972-10-10 Ncr Co Encapsulation process by complex coacervation using inorganic polyphosphates and organic hydrophilic polymeric material
US4273672A (en) 1971-08-23 1981-06-16 Champion International Corporation Microencapsulation process
US4010038A (en) 1974-04-10 1977-03-01 Kanzaki Paper Manufacturing Co., Ltd. Process for producing microcapsules
US4219439A (en) 1977-01-28 1980-08-26 Kanzaki Paper Manufacturing Co., Ltd. Method of making oil-containing microcapsules
US4222891A (en) 1977-08-17 1980-09-16 Kanzaki Paper Mfg. Co., Ltd. Method of making oil-containing microcapsules
US4217370A (en) 1977-08-25 1980-08-12 Blue Wing Corporation Lipid-containing feed supplements and foodstuffs
US4232084A (en) 1978-01-25 1980-11-04 Thalatta, Inc. Sheets containing microencapsulated color-coded micromagnets
US4891172A (en) 1979-10-15 1990-01-02 Mitsubishi Paper Mills, Ltd. Process for producing double-capsules
US4442051A (en) 1980-04-21 1984-04-10 Nicholas Proprietary Limited Encapsulation of indomethacin
US4485172A (en) 1981-01-19 1984-11-27 Cpc International Inc. Multistage process for the preparation of fats and oils
GB2091286B (en) 1981-01-19 1985-06-12 Cpc International Inc Preparation of fats and oils
GB2115768A (en) 1982-02-11 1983-09-14 Kms Fusion Inc Containment of hazardous fluids
JPS58149645U (en) 1982-03-31 1983-10-07
US4695466A (en) 1983-01-17 1987-09-22 Morishita Jintan Co., Ltd. Multiple soft capsules and production thereof
US4808408A (en) 1983-05-11 1989-02-28 Bend Research, Inc. Microcapsules prepared by coacervation
US4670247A (en) 1983-07-05 1987-06-02 Hoffman-Laroche Inc. Process for preparing fat-soluble vitamin active beadlets
US4923855A (en) 1983-07-08 1990-05-08 The William Seroy Group Synthetic GTF chromium material and process therefor
US4954492A (en) 1983-07-08 1990-09-04 The William Seroy Group Synthetic GTF chromium material for decreasing blood lipid levels and process therefor
US5194615A (en) 1983-07-08 1993-03-16 The William Seroy Group Synthetic GTF chromium nicotinate material and its preparation
US4744933A (en) 1984-02-15 1988-05-17 Massachusetts Institute Of Technology Process for encapsulation and encapsulated active material system
US4749620A (en) 1984-02-15 1988-06-07 Massachusetts Institute Of Technology Encapsulated active material system
US4963367A (en) 1984-04-27 1990-10-16 Medaphore, Inc. Drug delivery compositions and methods
JPS61172807U (en) 1985-04-18 1986-10-27
US5051304A (en) 1986-12-18 1991-09-24 Societe Anonyme: Mero Rousselot Satia Microcapsules based on gelatin and polysaccharides and process for obtaining same
US5156956A (en) 1987-03-04 1992-10-20 Ajinomoto Co., Inc. Transgultaminase
US4861627A (en) 1987-05-01 1989-08-29 Massachusetts Institute Of Technology Preparation of multiwall polymeric microcapsules
US5130061A (en) 1987-05-28 1992-07-14 Innova Di Ridolfi Flora & C. S.A.S. Process for the extraction of polyunsaturated fatty acid esters from fish oils
US4867986A (en) 1987-07-17 1989-09-19 Pharmachem Laboratories, Inc. Dry stabilized microemulsified omega-three acid-containing oils
EP0301777A1 (en) 1987-07-28 1989-02-01 Queen's University At Kingston Multiple membrane microencapsulation
US4895725A (en) 1987-08-24 1990-01-23 Clinical Technologies Associates, Inc. Microencapsulation of fish oil
WO1992011083A1 (en) 1987-09-28 1992-07-09 Redding Bruce K Jr Apparatus and method for making microcapsules
US5035896A (en) 1988-06-15 1991-07-30 Warner-Lambert Company Water insoluble drugs coated by coacervated fish gelatin
US5330778A (en) 1988-09-19 1994-07-19 Opta Food Ingredients, Inc. Hydrophobic protein microparticles
EP0434760B1 (en) 1988-09-19 1994-01-12 Opta Food Ingredients, Inc. Hydrophobic protein microparticles and preparation thereof
JPH0286743U (en) 1988-12-22 1990-07-10
US4946624A (en) * 1989-02-27 1990-08-07 The Procter & Gamble Company Microcapsules containing hydrophobic liquid core
US5059622A (en) 1989-08-29 1991-10-22 Biosyn, Inc. Method for reducing blood pressure levels in hypertensive persons
EP0416575A3 (en) 1989-09-05 1991-07-24 Medaphore Inc. Drug delivery compositions based on biological materials and methods for preparing such compositions
US5204029A (en) 1989-09-25 1993-04-20 Morgan Food Products, Inc. Methods of encapsulating liquids in fatty matrices, and products thereof
EP0426428B1 (en) 1989-10-31 1993-08-11 Warner-Lambert Company Encapsulated sweetener-flavour delivery system, and its production
WO1991006287A1 (en) 1989-11-06 1991-05-16 Enzytech, Inc. Protein microspheres and methods of using them
US5013569A (en) 1990-05-21 1991-05-07 Century Laboratories, Inc. Infant formula
US5456985A (en) 1990-06-13 1995-10-10 Zgoulli; Slim Microcapsules of oily liquid
US5356636A (en) 1991-12-14 1994-10-18 Basf Aktiengesellschaft Stable vitamin and/or carotenoid products in powder form, and the preparation thereof
US5759599A (en) 1992-03-30 1998-06-02 Givaudan Roure Flavors Corporation Method of flavoring and mechanically processing foods with polymer encapsulated flavor oils
US5573934A (en) 1992-04-20 1996-11-12 Board Of Regents, The University Of Texas System Gels for encapsulation of biological materials
EP0644771B2 (en) 1992-06-11 2006-12-06 Alkermes Controlled Therapeutics, Inc. Erythropoietin drug delivery system
US5700397A (en) 1992-06-16 1997-12-23 Fuji Oil Co., Ltd. Emulsifier, emulsion composition, and powder composition
US5603961A (en) 1992-10-01 1997-02-18 Tanabe Seiyaku Co., Ltd. Sustained release multi-core microsphere preparation and method for producing the same
US5378413A (en) 1993-01-21 1995-01-03 The United States Of America As Represented By The Secretary Of The Navy Process for preparing microcapsules having gelatin walls crosslinked with quinone
US5788991A (en) 1993-04-01 1998-08-04 Novartis Corporation Coated microparticle agglomerates
US6019998A (en) 1993-05-18 2000-02-01 Canon Kabushiki Kaisha Membrane structure
US5872140A (en) 1993-07-23 1999-02-16 Research Institute For Medicine And Chemistry, Inc. Vitamin D analogues
US5993851A (en) 1993-07-28 1999-11-30 Pharmaderm Laboratories, Ltd. Method for preparing biphasic multilamellar lipid vesicles
US5428014A (en) 1993-08-13 1995-06-27 Zymogenetics, Inc. Transglutaminase cross-linkable polypeptides and methods relating thereto
US5997863A (en) 1994-07-08 1999-12-07 Ibex Technologies R And D, Inc. Attenuation of wound healing processes
EP0745670B1 (en) 1994-10-11 2004-06-23 Ajinomoto Co., Inc. Stabilized transglutaminase and enzymatic preparation containing the same
US5827531A (en) 1994-12-02 1998-10-27 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Microcapsules and methods for making
US5603952A (en) 1994-12-30 1997-02-18 Tastemaker Method of encapsulating food or flavor particles using warm water fish gelatin, and capsules produced therefrom
US6020200A (en) 1995-03-03 2000-02-01 Metabolex, Inc. Encapsulation compositions and methods
US5670209A (en) 1995-04-24 1997-09-23 Brite-Line Technologies, Inc. High brightness durable retro-reflecting microspheres and method of making the same
WO1997013416A1 (en) 1995-10-12 1997-04-17 Mccormick & Company, Inc. Double encapsulation process and flavorant compositions prepared thereby
EP0782833B1 (en) 1996-01-05 2001-08-01 bautex Adolf Stöver Söhne KG Drawing device for a curtain
WO1997040701A1 (en) 1996-05-01 1997-11-06 Zymogenetics, Inc. Cross-linked protein gels and methods of making them
US5780056A (en) 1996-05-10 1998-07-14 Lion Corporation Microcapsules of the multi-core structure containing natural carotenoid
EP0821881B1 (en) 1996-08-01 2001-09-19 Ajinomoto Co., Inc. Milk whey protein-containing powder and processed food obtained by using the same
US5855826A (en) 1996-09-17 1999-01-05 Pacific Corporation Matrix-double encapsulation method and a cosmetic composition containing matrix-double capsules
US5766637A (en) 1996-10-08 1998-06-16 University Of Delaware Microencapsulation process using supercritical fluids
US6221401B1 (en) 1996-12-02 2001-04-24 The Regents Of The University Of California Bilayer structure which encapsulates multiple containment units and uses thereof
EP0856355B1 (en) 1997-01-31 2004-04-07 Givaudan SA Protein-encapsulated oil particles
US6325951B1 (en) 1997-01-31 2001-12-04 Givaudan Roure Flavors Corporation Enzymatically protein-encapsulating oil particles by complex coacervation
US6039901A (en) 1997-01-31 2000-03-21 Givaudan Roure Flavors Corporation Enzymatically protein encapsulating oil particles by complex coacervation
US6063820A (en) 1997-03-20 2000-05-16 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Medical food for diabetics
US6630157B1 (en) 1997-07-22 2003-10-07 Viatris Gmbh & Co. Kg. Therapeutic and dietary compositions containing essential fatty acids and bioactive disulphides
EP0897970B1 (en) 1997-08-22 2004-09-29 Unilever N.V. Process for the production of stanol esters
US6106875A (en) 1997-10-08 2000-08-22 Givaudan Roure (International) Sa Method of encapsulating flavors and fragrances by controlled water transport into microcapsules
US6274174B1 (en) 1997-10-31 2001-08-14 Nisshinbo Industries, Inc. Aggregates of spherical multivalent metal alginate microparticles and methods of making them
CA2318539A1 (en) 1998-01-17 1999-07-22 Henkel Kommanditgesellschaft Auf Aktien Lipoprotein creams
US6234464B1 (en) 1998-07-08 2001-05-22 K.D. Pharma Bexbech Gmbh Microencapsulated unsaturated fatty acid or fatty acid compound or mixture of fatty acids and/fatty acid compounds
EP0982038B1 (en) 1998-08-24 2003-01-08 N-Zyme BioTec GmbH Stable powdery vitamin and carotenoide containing compositions and process to prepare them
US6417233B1 (en) 1998-10-21 2002-07-09 Sigma-Tau Healthscience S.P.A. Ubiguinone-containing composition suitable for promoting enhanced intramitochondrial transportation of ubiguinones and methods of using same
US6103378A (en) 1998-11-23 2000-08-15 The Mead Company Capsules having discrete solvent/color former and diluent capsule encapsulated phases
US6482433B1 (en) 1999-06-30 2002-11-19 Givaudan Sa Encapsulation of active ingredients
US6534091B1 (en) 1999-07-02 2003-03-18 Cognis Iberia S. L. Microcapsules
US6528165B2 (en) 1999-08-17 2003-03-04 Luminex Corporation Encapsulation of discrete quanta of fluorescent particles
US6328995B1 (en) 1999-09-24 2001-12-11 Basf Aktiengesellschaft Stable vitamin and/or carotenoid products in powder form and process for their production
US6500463B1 (en) 1999-10-01 2002-12-31 General Mills, Inc. Encapsulation of sensitive components into a matrix to obtain discrete shelf-stable particles
EP1237423B1 (en) 1999-11-18 2004-08-04 Quest International B.V. Stable, spray-dried composition in a carbohydrate substrate and process for obtaining said composition
EP1116516A1 (en) 2000-01-13 2001-07-18 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Templating of solid particles by polymer multilayers
US6534926B1 (en) 2000-04-12 2003-03-18 Tmc Enterprises, A Division Of Tasco Industries, Inc. Portable fluorescent drop-light
WO2001080656A1 (en) 2000-04-26 2001-11-01 Skånemejerier Ek.För. Lipid composition and use thereof
US6534094B2 (en) 2000-05-03 2003-03-18 Eriochem S.A. Manufacturing process of microcapsules for sustained release of water soluble peptides
US20020031553A1 (en) 2000-05-03 2002-03-14 Nora Moyano Manufacturing process of microcapsules for sustained release of water soluble peptides
JP2002028473A (en) 2000-07-18 2002-01-29 Nippon Capsule Products:Kk Method for manufacturing microcapsule film of which is made airtight
US6365176B1 (en) 2000-08-08 2002-04-02 Functional Foods, Inc. Nutritional supplement for patients with type 2 diabetes mellitus for lipodystrophy
US6441050B1 (en) 2000-08-29 2002-08-27 Raj K. Chopra Palatable oral coenzyme Q liquid
EP1357977B1 (en) 2000-09-21 2004-07-21 Nutrition 21, Inc. Chromium containing compositions for the treatment of diabetes, the reduction of body fat, improvement of insulin sensitivity and reduction of hyperglycemia and hypercholesteremia
US20030091654A1 (en) 2000-09-21 2003-05-15 Katz David P. Methods for the treatment of diabetes, the reduction of body fat, improvement of insulin sensitivity, reduction of hyperglycemia, and reduction of hypercholesterolemia with chromium complexes, conjugated fatty acids, and/or conjugated fatty alcohols
US6300377B1 (en) 2001-02-22 2001-10-09 Raj K. Chopra Coenzyme Q products exhibiting high dissolution qualities
WO2002096408A1 (en) 2001-05-30 2002-12-05 Laxdale Limited Coenzyme q and eicosapentaenoic acid (epa)
US20030078617A1 (en) 2001-07-16 2003-04-24 Schwartz Herbert E. Unitary surgical device and method
US20030044380A1 (en) 2001-07-19 2003-03-06 Zhu Yong Hua Adhesive including medicament
CA2447002C (en) 2001-10-11 2012-05-29 Appleton Papers Inc. Microcapsules having improved printing and efficiency
US6544926B1 (en) 2001-10-11 2003-04-08 Appleton Papers Inc. Microcapsules having improved printing and efficiency
US20030133886A1 (en) 2001-11-15 2003-07-17 Xerox Corporation Photoprotective and lightfastness-enhancing siloxanes
US6652891B2 (en) 2001-12-12 2003-11-25 Herbasway Laboratories, Llc Co-enzyme Q10 dietary supplement
US6974592B2 (en) 2002-04-11 2005-12-13 Ocean Nutrition Canada Limited Encapsulated agglomeration of microcapsules and method for the preparation thereof
US20050019416A1 (en) 2002-04-11 2005-01-27 Ocean Nutrition Canada Ltd. Encapsulated agglomeration of microcapsules and method for the preparation thereof
US20030193102A1 (en) * 2002-04-11 2003-10-16 Nianxi Yan Encapsulated agglomeration of microcapsules and method for the preparation thereof
WO2003086104A1 (en) 2002-04-11 2003-10-23 Ocean Nutrition Canada Ltd. Encapsulated agglomeration of microcapsules and method for the preparation thereof
US7727629B2 (en) 2002-04-11 2010-06-01 Ocean Nutrition Canada Limited Encapsulated agglomeration of microcapsules and method for the preparation thereof
WO2003106014A1 (en) 2002-06-14 2003-12-24 Nizo Food Research B.V. Complex coacervates containing whey proteins
WO2003105606A1 (en) 2002-06-18 2003-12-24 Martek Biosciences Corporation Stable emulsions of oils in aqueous solutions and methods for producing same
US20050249952A1 (en) * 2002-09-04 2005-11-10 Southwest Research Institute Microencapsulation of oxygen or water sensitive materials
US20050067726A1 (en) * 2002-11-04 2005-03-31 Nianxi Yan Microcapsules having multiple shells and method for the preparation thereof
WO2004041251A1 (en) 2002-11-04 2004-05-21 Ocean Nutrition Canada Limited Microcapsules having multiple shells and method for the preparation thereof
JP2006506410A (en) 2002-11-04 2006-02-23 オーシャン・ニュートリション・カナダ・リミテッド Microcapsules and methods for their preparation having a plurality of shells
US20040106591A1 (en) 2002-11-22 2004-06-03 Pacioretty Linda M. Compositions and methods for the treatment of HIV-associated fat maldistribution and hyperlipidemia
WO2004054702A8 (en) 2002-12-18 2005-10-06 Lever Hindustan Ltd Complex coacervate encapsulate comprising lipophilic core
EP1430947A1 (en) 2002-12-21 2004-06-23 Cognis Iberia, S.L. Multicompartment microparticles with liquid crystalline cores
US20070027028A1 (en) 2003-08-14 2007-02-01 Pears David A Microencapsulated catalyst-ligand system, methods of preparation and methods of use thereof
US20050118285A1 (en) 2003-10-23 2005-06-02 L'oreal O/W emulsion containing aloe vera, uses thereof, method for making
US6972592B2 (en) 2003-11-24 2005-12-06 Lsi Logic Corporation Self-timed scan circuit for ASIC fault testing
US20070224216A1 (en) 2004-05-04 2007-09-27 Jane Teas Methods and Compositions Related to Antiviral Therapy Using Algae and Cyanobacteria
US6969530B1 (en) 2005-01-21 2005-11-29 Ocean Nutrition Canada Ltd. Microcapsules and emulsions containing low bloom gelatin and methods of making and using thereof
US8039030B2 (en) 2005-07-01 2011-10-18 Martek Biosciences Corporation Microwaveable popcorn and methods of making
US20090274791A1 (en) 2005-07-07 2009-11-05 Mattson Pete H Food Articles With Delivery Devices and Methods for the Preparation Thereof
US20070059340A1 (en) 2005-09-09 2007-03-15 Anthony Bello Omega-3 Fatty Acids Encapsulated In Zein Coatings and Food Products Incorporating the Same
US20070078071A1 (en) 2005-09-30 2007-04-05 Kaiping Lee Spray dry capsule products and methods for preparing and using same
WO2007055815A1 (en) 2005-10-31 2007-05-18 General Mills, Inc. Encapsulation of readily oxidizable components
WO2007054207A1 (en) 2005-11-14 2007-05-18 Unilever N.V. Sterilised nutritional beverage
US20070141211A1 (en) 2005-12-16 2007-06-21 Solae, Llc Encapsulated Phospholipid-Stabilized Oxidizable Material
US20100055281A1 (en) 2006-04-07 2010-03-04 Ocean Nutrition Canada Limited Emulsions and Microcapsules With Substances Having Low Interfacial Tension, Methods of Making and Using Thereof
US20100173002A1 (en) 2006-06-05 2010-07-08 Jin Yulai Microcapsules with improved shells
JP5292899B2 (en) 2008-04-02 2013-09-18 セイコーエプソン株式会社 Fluid ejection device
JP5394273B2 (en) 2010-02-03 2014-01-22 本田技研工業株式会社 Hydrogen absorption material and a manufacturing method thereof
JP5828234B2 (en) 2011-06-29 2015-12-02 株式会社寺岡精工 Empty container collection device

Non-Patent Citations (121)

* Cited by examiner, † Cited by third party
Title
Appel et al., "Does supplementation of diet with ‘fish oil’ reduce blood pressure? A meta-analysis of controlled clinical trials," Arch Intern Med., 153(12):1429-1438 (1993).
Appel et al., "Does supplementation of diet with 'fish oil' reduce blood pressure? A meta-analysis of controlled clinical trials," Arch Intern Med., 153(12):1429-1438 (1993).
Barrow et al., "Stabilization of highly unsaturated fatty acids and delivery into foods," Lipid Technology, 9(5):108-111 (2007).
Beestman, "Microencapsulation of Solid Particles," Chemical Abstract, Abstracts of Papers, 220th ACS National Meeting, Washington, DC, United States, Aug. 20-24, 2000, AGRO-037. CODEN: 69FZC3 AN 2000:793223.
Boh et al., "Microcapsule Applications: Patent and Literature Analysis," MML Series, 6:85-156 (2003).
Bonnet et al., Ullmann's Encyclopedia of Industrial Chemistry, vol. II, p. 668, right col. (2003).
Borghi, "Omega-3 LC PUFAs, A new solution for pasterurized milk enrichment," Wellness Foods Europe, pp. 25-26 (May 2005).
Calon et al., "Docosahexaenoic acid protects from dentritic pathology in an Alzeheimer's Disease mouse model," Neuron, 43:633-645 (2004).
Choi et al., "Physicochemical and sensory characteristics of fish gelatin," J. Food Sci. Food Chemistry and Toxicology, 65:194-199 (2000).
Chourpa, Igor, et al., "Conformational Modifications of alpha Gliadin and Globulin Proteins upon Complex Coacervates Formation with Gum Arabic as Studied by Raman Microspectroscopy," Biomacromolecules, vol. 7, 2006, pp. 2616-2623.
Chourpa, Igor, et al., "Conformational Modifications of α Gliadin and Globulin Proteins upon Complex Coacervates Formation with Gum Arabic as Studied by Raman Microspectroscopy," Biomacromolecules, vol. 7, 2006, pp. 2616-2623.
Dyerberg et al., "In Omega-3 fatty acids: prevention and treatment of vascular disease," Kristensen et al., Eds. Bi. & Gi Publ., Verona-Springer-Verlag, London, pp. 217226 (1995).
Encyclopedia of Pharmaceutical Technology, "Micoencapsulation," Editors; James Swarbrick and James C. Boylan, Marcel Dekker, Inc., New York, vol. 9, pp. 423-441, 1994.
European Patent Office European Search Report for 06020381.7 dated Apr. 10, 2007.
European Search Authority International Search Report for PCT/IB2006/001214 and Written Opinion mailed Feb. 8, 2007.
Examination report for Application No. 07825594.0 dated Mar. 30, 2011.
Examination report for Application No. 2003-583137 dated May 10, 2011.
Examination report for Application No. 200780019734.2 dated May 6, 2011.
Examination report for Application No. 200780029069.5 dated Feb. 24, 2011.
Examination report for Application No. 200880007740.0 dated Mar. 23, 2011.
Examination Report for Application No. 565606 dated May 13, 2010.
Examination Report for Application No. 573327 dated Nov. 16, 2011.
Examination Report for Application No. 596403 dated Nov. 16, 2011.
Examination Report for Application No. AU 2008205325 dated Jun. 22, 2012.
Examination Report for Application No. CL 2008-63 dated May 15, 2012.
Examination Report for Application No. JP 2003-583137 dated Aug. 24, 2012.
Examination Report for Application No. JP 2009-523371 dated Sep. 24, 2012.
Examination Report for Application No. JP 2009-545586 dated Sep. 19, 2012.
Examination Report for Application No. JP 2010-190957 dated Oct. 16, 2012.
Examination report for Application No. MX/a/2008/012967 dated Apr. 27, 2011.
Examination Report for Application No. NZ 600903 dated Jul. 3, 2012.
Extended European Search Report for Application No. EP 07825594.0 dated Aug. 31, 2011.
Fong, "Microencapsulation by solvent and organic phase separation processes," Controlled Release Systems: Fabrication Technology, Hsieh Ed., CRC Press, New York, pp. 99-105 (1988).
GISSI-Prevenzione Investigators, "Dietary supplementation with Omega-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial," Lancet, 354:447-455 (1999).
Goyer, "Toxic effects of metals," Casarett and Doull's Toxicology, Amdur et al., Eds., 4th ed., Pergamon Press, New York, pp. 638-639 (1991).
Harris, "Extending the cardiovascular benefits of Omega-3 fatty acids," Curr. Atheroscler Rep., 7:375-380 (2005).
Haug et al., "Physical and rheological properties of fish gelatin compared to mammalian gelatin," Food Hydrocolloids, 18:203-213 (2004).
Holub, "Clinical Nutrition: 4 Omega-3 fatty acids in cardiovascular care," CMAJ, 166(5):608-615 (2002).
http://en.wikipedia.org/wiki/morula, 2011.
http://www.advancedfertility.com/4cell.htm, 2011.
http://www.advancedfertility.com/8cell.htm, 2011.
http://www.advancedfertility.com/morula.htm, 2011.
Ijichi et al., "Multi-Layered GelatinAcacia Microcapsules by Complext Coacervation Method," J. of Chem Eng. of Japan., 30(5):793-798 (1997).
Jizomoto, Hiroaki, "Phase Separation Induced in Gelatin-Base Coacervation Systems by Addition of Water-Soluble Nonionic Polymers I: Microencapsulation," Journal of Pharmaceutical Sciences, vol. 73, No. 7, 1984, pp. 879-882.
Kage et al., "Microencapsulation of mono-dispersed droplets by complex coacervation and membrane thickness of generated capsules," Chemical Abstract No. Accession 615273 (2000).
Kas et al., "Microencapsulation using coacervatoin/phrase separation," In Handbook of Pharmaceutical Controlled Release Technology, Wise Ed., Marcel Dekker Inc., New York, pp. 301-328 (2000).
Kondo et al., "Microencapsulation utilizing phase separation from an aqueous solution system," Microcapsule Processing and Technology, Marcel Dekker Inc., New York, pp. 70-95 (1979).
Kris-Etherton et al., "Fish consumption, fish oil, Omega-3 fatty acids and cardiovascular disease," The American Heart Association Scientific Statement, 106(21):2747-2757 (Nov. 2002).
Leclercq et al., "Formation and characterization of microcapsules by complex coacervation with liquid or solid aroma cores," Flavour Fragr. J., 24:17-24 (2009).
Limmer, "Remington: The Science and Practice of Pharmacy," p. 332, left col. (2000).
Magdassi et al., "Microencapsulation of Oil-in-Water Emulsions by Proteins," Microencapsulation—Methods and Industrial Applications, edited by Simon Benita, Marcel Dekker, Inc., New York, pp. 21-33 (1996).
Marcus et al., "The Vitamins," Goodman and Gilman's the Pharmacological Basis of Therapeutics, McGraw-Hill, Inc., New York, pp. 1524-1527 (1990).
Mori et al., "Purified eicosapentaenoic and docosapentaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hypelipidemic men," Am. J. Clin. Nutr., 71:1085-1094 (2000).
Muskiet et al., "Is docosahexaenoic acid (DHA) essential? Lessons from DHA status regulation, our ancient diet, epidemiology and randomized controlled trials," J. Nutr., 134(1):183-186 (2004).
Notice of Allowance for U.S. Appl. No. 11/227,961 dated Jun. 14, 2011.
Office Action for Application No. 07754635.6 dated Aug. 26, 2011.
Office Action for Application No. 07825594.0 dated Mar. 30, 2011.
Office Action for Application No. 08713076.1 dated Sep. 21, 2011.
Office Action for Application No. 200680032544.X dated Oct. 20, 2011.
Office Action for Application No. 200780019734.2 dated May 6, 2011.
Office Action for Application No. 200780029069.5 dated Feb. 24, 2011.
Office Action for Application No. 2008-520263 dated Feb. 22, 2011.
Office Action for Application No. 200880007740.0 dated Mar. 23, 2011.
Office Action for Application No. 7007996/2005 dated Nov. 4, 2011.
Office Action for Application No. AU 2007238985 dated Dec. 5, 2011.
Office Action for Application No. AU 2007282922 dated Mar. 2, 2012.
Office Action for Application No. CN 200780019734.2 dated Apr. 25, 2012.
Office Action for Application No. CN 200780029069.5 dated Apr. 27, 2012.
Office Action for Application No. CN 200880007740.0 dated Mar. 16, 2012.
Office Action for Application No. EP 06773967.2 dated May 18, 2012.
Office Action for Application No. EP 07754635.6 dated Dec. 21, 2009.
Office Action for Application No. EP 07754635.6 dated Mar. 6, 2012.
Office Action for Application No. EP 07825594.0 dated Aug. 31, 2011.
Office Action for Application No. EP 08713076.1 dated Feb. 18, 2013.
Office Action for Application No. EP 11196119.9 dated Mar. 1, 2012.
Office Action for Application No. JP 2003-583137 dated Jan. 24, 2012.
Office Action for Application No. JP 2009-504244 dated Feb. 20, 2011.
Office Action for Application No. KR 1020097000087 dated Oct. 18, 2013 (English Translation).
Office Action for Application No. KR 10-2011-7022451 dated Dec. 22, 2011.
Office Action for Application No. MX/a/2008/000210 dated Feb. 20, 2012.
Office Action for Application No. MX/a/2008/000210 dated Oct. 20, 2011.
Office Action for Application No. MX/a/2008/015556 dated Mar. 15, 2012.
Office Action for Application No. NZ 572529 dated May 21, 2010.
Office Action for Application No. NZ 572529 dated Oct. 22, 2010.
Office Action for Application No. NZ 573327 dated Dec. 8, 2011.
Office Action for Application No. NZ 578872 dated Nov. 11, 2011.
Office Action for Application No. PE 000110-2008 dated Feb. 29, 2012.
Office Action for U.S. Appl. No. 11/435,605 dated Jan. 24, 2011.
Office Action for U.S. Appl. No. 11/435,605 dated Sep. 2, 2010.
Office Action for U.S. Appl. No. 11/918,150 dated Nov. 16, 2011.
Office Action for U.S. Appl. No. 11/988,320 dated Sep. 1, 2011.
Office Action for U.S. Appl. No. 12/308,045 dated Feb. 17, 2012.
Office Action for U.S. Appl. No. 12/308,045 dated Nov. 16, 2012.
Office Action for U.S. Appl. No. 12/308,045 dated Oct. 7, 2013.
Office Action for U.S. Appl. No. 12/308,045 dated Sep. 9, 2011.
Office Action for U.S. Appl. No. 12/522,826 dated Aug. 7, 2012.
Office Action for U.S. Appl. No. 12/522,826 dated Feb. 28, 2013.
Office Action for U.S. Appl. No. 12/522,826 dated Jul. 2, 2013.
Office Action for U.S. Appl. No. 12/768,152 dated Jul. 25, 2013.
Office Action for U.S. Appl. No. 12/768,152 dated Sep. 12, 2012.
O'Keefe et al., "Omega-3 acids: Time for clinical implementation?" Am. J. Cardiology, 85:1239-1241 (2002).
Onuki et al., "In vivo effects of highly purified docosahexaenoic acid on rectal insulin absorption," Int. J Pharm., 198:147-156 (2000).
Ovide-Borodeaux et al., "Docosahexaenoic acid affects insulin-deficiency and insul resistant-induced alterations in cardiac mitochondria," Am. J. Physiool. Regul. Integr. Comp. Physiol., 286:R519-R527 (2003).
Radack et al., "The effects of low doses of Omega-3 fatty acid supplementation on blood pressure in hypertensive subjects: a randomized controlled trial," Arch. Intern. Med., 151:1173-1180 (1991).
Reasons for Submission on behalf of Japan Capsular Products Inc. filed in Japanese Patent Application No. 2003-583137 on Nov. 26, 2010.
Recommended Daily Allowances, Ninth Revised Edition, The Natural Academy of Sciences, p. 160 (1980).
Response to Office Action for NZ 572529 dated Oct. 1, 2010.
Response to Office Action for U.S. Appl. No. 11/435,605 dated Apr. 13, 2011.
Response to Office Action for U.S. Appl. No. 11/435,605 dated Nov. 5, 2010.
Response to Office Action for U.S. Appl. No. 12/308,045 dated Aug. 7, 2012.
Response to Opposition for Application No. EP06020381.7 dated Jun. 29, 2011.
Schrooyen et al., Microencapsulation: its application in nutrition, Proceedings of the Nutrition Society, 60:475-479 (2001).
Soper, "Utilization of coacervated flavors," Encapsulation and Controlled Release of Food Ingredients, Risch and Reineccius Ed., ACS Symposium Series 590, Washington, D.C., pp. 104-112 (1995).
Sparks, "Microencapsulation," Kirk-Othmer, Encyclopedia of Chemical Technology, vol. 15, 3rd Ed., John Wiley & Sons Inc., New York, pp. 470-793 (1981).
Sugano et al., "Balanced intake of polyunsaturated fatty acids for health benefits," J. Oleo. Sci., 50(5):305-311 (2001).
Summons to Attend Oral Proceedings for Application No. EP 03711759.5 dated Jan. 4, 2012.
Summons to Attend Oral Proceedings for Application No. EP 06020381.7 dated Jan. 4, 2012.
Thimma et al., "Study of complex coacervation of gelatin with sodium carboxymethyl guar gum: Microencapsulation of close oil and sulphamethoxazole," J. Microencapsulation, 20(2):203-210 (2003).
Webb, "Alternative sources of Omega-3 fatty acids," Natural Foods Merchandiser, XXVI(8):40-44 (2005).
Whorton et al., "Evaluation of the mechanisms associated with the release of encapsulated flavor form maltodextrin matrices," Encapsulation and Controlled Release of Food Ingredients, Risch and Reineccius Ed., ACS Symposium Series 590, Washington, D.C., pp. 143-160 (1995).
Yoshida et al., "Manufacture of microcapsules from complex coacervation processes," Chemical Abstract, Accession No. 140735 (1990).

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